体内外研究羟基胆固醇硫酸基转移酶（SULT2B1b）及其硫化产物对肝脏增生的影响及机制
|
摘要
前言
胞浆硫酸基转移酶(SULT)2Blb能够催化胆固醇及羟基胆固醇的3β-羟基硫酸化,其催化25-羟化胆固醇(25HC)硫酸化反应的主要产物为3-硫酸-25-羟化胆固醇(25HC3S)。研究发现SULT2B1b能够抑制羟基胆固醇对肝X受体(LXRs)的激活,并且其硫酸化产物可以通过抑制LXR/SREBPs信号转导通路降低细胞内脂质水平。而LXRs信号途径的激活对细胞增殖起负调节作用。因此SULT2B1b及其硫化产物25HC3S可能对肝脏增生起重要作用。本实验中,我们在小鼠正常肝脏、原代大鼠肝脏细胞(PRH)以及小鼠肝脏部分切除术(PH)模型中研究SULT2B1b对肝脏增生的作用及机制,并在小鼠正常肝脏中检测SULT2B1b的硫化产物25HC3S对肝脏增生的影响及相关机制。
第一部分体内外研究SULT2B1b对肝脏增生的影响
第一节SULT2B1b对小鼠肝脏增生以及原代大鼠肝细胞(PRH)生长的影响及相关机制
目的：探索SULT2B1b对小鼠肝脏以及PRH增生的影响及机制。
方法：将含有SULT2B1b基因的腺病毒感染C57BL/6(?)、鼠及PRH后,运用PCNA免疫组织化学染色法检测肝脏增生状态；应用免疫荧光双染法定位肝脏内SULT2B1b与PCNA的表达；采用siRNA干扰技术反面验证SULT2B1b对肝细胞生长的影响；通过实时定量PCR和免疫印迹的方法检测基因表达水平。
结果：体内实验表明小鼠肝脏组织中的PCNA阳性细胞率随SULT2B1b表达水平的升高而明显增加,并存在剂量和时间依赖性；肝脏内几乎所有存在PCNA表达的细胞核均伴随SULT2B1b在细胞质的高表达,而没有SULT2B1b表达的细胞内也检测不到PCNA的表达。在SULT2B1b相对高表达的PRH内,采用RNA干扰技术抑制SULT2B1b基因的表达,引起细胞周期调节基因CDK2, FoxM1b,与Cyclin A的表达明显降低。此外,LXR人工合成激动剂T0901317可有效阻断体内夕(?) SULT2B1b所诱导的PCNA鞥表达升高。
结论：SULT2B1b能够通过抑制LXR信号转导通路的活性促进体内外肝细胞增生。
第二节在部分肝切除术(PH)后的小鼠模型中研究SULT2B1b对肝脏再生的影响及机制
目的：研究SULT2B1b对肝脏再生的影响及机制。
方法：在C57BL/6小鼠体内建立肝脏PH再生模型,并通过尾静脉注射含有SULT2B1b基因的腺病毒或对照病毒；病毒感染5天后,应用免疫组织化学的方法分析肝再生过程中的PCNA阳性细胞率；采用HPLC技术检测肝脏内羟基胆固醇的变化；运用实时定量PCR和免疫印迹法检测基因表达水平。
结果：SULT2B1b过表达的小鼠肝脏恢复较快,约于术后三天恢复到肝脏原始大小的80%,而对照组需要将近5天达到同样水平。SULT2B1b过表达增加了肝脏再生过程中的PCNA阳性细胞率以及增生相关基因的表达水平；降低了肝脏内的羟基胆固醇含量以及LXR信号转导通路下游基因SREBP-1和ABCA1的表达水平。
结论：SULT2B1b能够通过抑制羟基胆固醇/LXR信号转导通路促进肝脏损伤后的再生。
第二部分在小鼠体内研究羟基胆固醇硫化物对肝脏增生的影响及其相关机制
目的：探索SULT2B1b的硫化产物(25HC3S)对小鼠体内肝脏增生的影响及机制
方法：向C57BL/6小鼠尾静脉直接注射3-硫酸-25-羟化胆固醇(25HC3S)化合物,或向感染了腺病毒(Ad-SULT2B1b)两天后的C57BL/6小鼠腹腔内注射25HC,建立高浓度外源性或内源性25HC3S的小鼠模型；应用[3H]标记25HC3S并经尾静脉注射小鼠体内,追踪25HC3S在各组织器官中的分布及其药代动力学：采用实时定量PCR,细胞周期PCR芯片以及免疫印迹法检测相关基因的表达水平。以PCNA为增生标记,应用免疫组织化学技术分析肝脏中PCNA的阳性细胞数。
结果：外源性25HC3S给药后在小鼠体内广泛分布于各组织器官,并在注射后48小时左右减至初始剂量的一半25HC3S的增加上调了肝脏内增生相关基因Wtl, Pcna,cMyc, cyclin A, FoxM1b, CDC25b的表达,却下调了细胞周期停滞基因Check2以及凋亡诱导基因Apafl的表达；无论外源性给药还是内源性合成,25HC3S的应用均有效增加了PCNA阳性细胞率,降低了LXR信号转导通路下游基因如ABCA1和SREBP-lc的表达；最后,LXR的人工合成激动剂T0901317的应用有效阻止了25HC3S诱导的PCNA表达升高。
结论：25HC3S能够促进肝脏增生。羟基胆固醇硫酸化通过对LXR信号转导通路的抑制为肝脏增生的研究提供了新的靶点。
综上所述,羟基类固醇硫酸基转移酶(SULT2B1b)通过硫酸化羟基胆固醇,增加硫化羟基胆固醇(25HC3S)的产生,抑制LXR信号转导通路活性,从而促进肝脏增生以及肝脏损伤后的再生恢复。
Introduction
Cytosolic sulfotransferase (SULT)2Blb catalyzes sulfation of oxysterol and hydroxysterol, including25-hydroxycholesterol (25HC). The main product of this reaction is25-hydroxycholesterol-3-sulfate (25HC3S). It has been reported that SULT2Blb inhibits the activation of oxysterol to Liver X Receptors (LXRs) and25HC3S decreases cellular lipids via suppressing LXR/sterol regulatory element-binding proteins (SREBPs) signaling in THP-1derived macrophages. Furthermore, LXR activation has been identified as anti-proliferative factor in several cellular and animal models. Therefore, the key enzyme for the biosynthesis of25HC3S, SULT2Blb, may play a crucial role in regulating liver proliferation. In the present study, we investigated the effects and mechanisms of SULT2B1b and its product-25HC3S in liver proliferation in mouse liver with or without partial hepatectomy (PH) and in primary rat hepatocyte (PRH).
Part Ⅰ. Effect of SULT2Blb on hepatic proliferation in vivo and in vitro
Section I:The effect and mechanism of cytosolic sulfotransferase2Blb (SULT2B1b) on proliferation in mouse liver tissues and in primary rat hepatocyte (PRH)
Aims:To investigate the effect and the underlying mechanism of SULT2Blb on liver proliferation in vivo and in vitro.
Methods:Primary rat hepatocyte (PRH) and C57BL/6mice were infected with adenovirus encoding SULT2B1b. Liver proliferation was determined by measuring the proliferating cell nuclear antigen (PCNA) immunostaining labeling index. The correlation between the SULT2B1b and PCNA expression in mouse liver tissues were determined by double immunofluorescence. Gene expressions were evaluated by quantitative real-time PCR and western blot analysis.
Results:SULT2B1b overexpression in mouse liver tissues increased PCNA-positive cells in a dose-and time-dependent manner. The expression of PCNA in mouse liver tissues was almost observed in the SULT2Blb-transgenic cells, while PCNA is undetectable in the cells without SULT2Blb overexpression. Small interference RNA-SULT2B1b significantly inhibited cell cycle regulatory gene expressions in primary rat hepatocytes (PRH). LXR activation by T0901317, effectively suppressed SULT2B1b-induced gene expression both in vivo and in vitro.
Conclusions:SULT2B1b may promote hepatocyte proliferation via inactivating oxysterol/LXR signaling in vivo and in vitro.
Section Ⅱ:Effect of SULT2Blb on liver regeneration following mouse partial hepatectomy (PH)
Aims:To evaluate the effect and mechanism of SULT2B11b on liver regeneration.
Methods:C57BL/6mice were performed PH and infected with Ad-SULT2B1b or Ad-control for5days. Liver proliferation was determined by measuring the PCNA immunostaining labeling index. Levels of hepatic oxysterols were analysed by HPLC. Gene expressions were evaluated by quantitative real-time PCR and western blot analysis.
Results:C57BL/6mice infected with Ad-SULT2Blb exhibited a faster liver re-growth, taking3days to reach80%of their original liver mass, while control mice took nearly5days to reach this liver mass. Following PH, SULT2B1b overexpression resulted in an apparent reduction of oxysterols coupled with a further down-regulation of the LXR signaling while the expression of proliferative genes were further increased. T0901317, a synthetic agonist of LXR, completely blocked SULT2B1b-induced increases in PCNA protein and decreases in the LXR signaling pathway.
Conclusions:Increases in SULT2B1b promote Liver regeneration after PH via inhibiting LXR signaling.
Part II. Effect of cholesterol metabolite (25HC3S) on hepatic proliferation in mice
Aims:To determine the effects of exogenous or endogenous25HC3S on the hepatic proliferation in vivo of C57BL/6mice.
Methods:C57BL/6mice were injected with exogenous25HC3S, or infected with adenovirus encoding SULT2B1b, combined by25HC administration to get endogenous25HC3S. The biodistribution of exogenous25HC3S in tissues and the formation of endogenous25HC3S in liver was examined by [3H]-25HC3S radioactivity analysis. Hepatic gene expressions were evaluated by quantitative real-time PCR, cell cycle RT2ProfilerTM PCR array, and western blot analysis. Liver proliferation was determined by measuring the proliferating cell nuclear antigen (PCNA) immunostaining labeling index (LI).
Results:Following exogenous administration,25HC3S had a48h half life in circulation and widely distributed in mouse tissues.25HC3S or overexpression of SULT2B1b plus administration of25HC (endogenous25HC3S) significantly up-regulated the proliferation gene expression of Wt1, Pcna, cMyc, cyclin A, FoxM1b, and CDC25b in a dose-dependent manner in liver; substantially down-regulated the expression of cell cycle arrest gene Chek2and apoptotic gene Apaf1. Both exogenous and endogenous administration of25HC3S significantly induced hepatic DNA replication as measured by immunostaining of the PCNA labeling index and associated with reduction in expression of LXRs response genes, such as ABCA1and SREBPlc. LXR activation by synthetic agonist T0901317effectively blocked the25HC3S-induced hepatic proliferation.
Conclusions:25HC3S is a potent regulator of proliferation and the oxysterol sulfation may represent a novel regulatory pathway in liver proliferation via inactivating LXR signaling.
In summary,25HC sulfation by SULT2B1b may promote hepatic proliferation and regeneration by down-regulation of LXR signaling pathway in vitro PRH and in vivo mouse liver tissues.
胞浆硫酸基转移酶(SULT)2Blb能够催化胆固醇及羟基胆固醇的3β-羟基硫酸化,其催化25-羟化胆固醇(25HC)硫酸化反应的主要产物为3-硫酸-25-羟化胆固醇(25HC3S)。研究发现SULT2B1b能够抑制羟基胆固醇对肝X受体(LXRs)的激活,并且其硫酸化产物可以通过抑制LXR/SREBPs信号转导通路降低细胞内脂质水平。而LXRs信号途径的激活对细胞增殖起负调节作用。因此SULT2B1b及其硫化产物25HC3S可能对肝脏增生起重要作用。本实验中,我们在小鼠正常肝脏、原代大鼠肝脏细胞(PRH)以及小鼠肝脏部分切除术(PH)模型中研究SULT2B1b对肝脏增生的作用及机制,并在小鼠正常肝脏中检测SULT2B1b的硫化产物25HC3S对肝脏增生的影响及相关机制。
第一部分体内外研究SULT2B1b对肝脏增生的影响
第一节SULT2B1b对小鼠肝脏增生以及原代大鼠肝细胞(PRH)生长的影响及相关机制
目的：探索SULT2B1b对小鼠肝脏以及PRH增生的影响及机制。
方法：将含有SULT2B1b基因的腺病毒感染C57BL/6(?)、鼠及PRH后,运用PCNA免疫组织化学染色法检测肝脏增生状态；应用免疫荧光双染法定位肝脏内SULT2B1b与PCNA的表达；采用siRNA干扰技术反面验证SULT2B1b对肝细胞生长的影响；通过实时定量PCR和免疫印迹的方法检测基因表达水平。
结果：体内实验表明小鼠肝脏组织中的PCNA阳性细胞率随SULT2B1b表达水平的升高而明显增加,并存在剂量和时间依赖性；肝脏内几乎所有存在PCNA表达的细胞核均伴随SULT2B1b在细胞质的高表达,而没有SULT2B1b表达的细胞内也检测不到PCNA的表达。在SULT2B1b相对高表达的PRH内,采用RNA干扰技术抑制SULT2B1b基因的表达,引起细胞周期调节基因CDK2, FoxM1b,与Cyclin A的表达明显降低。此外,LXR人工合成激动剂T0901317可有效阻断体内夕(?) SULT2B1b所诱导的PCNA鞥表达升高。
结论：SULT2B1b能够通过抑制LXR信号转导通路的活性促进体内外肝细胞增生。
第二节在部分肝切除术(PH)后的小鼠模型中研究SULT2B1b对肝脏再生的影响及机制
目的：研究SULT2B1b对肝脏再生的影响及机制。
方法：在C57BL/6小鼠体内建立肝脏PH再生模型,并通过尾静脉注射含有SULT2B1b基因的腺病毒或对照病毒；病毒感染5天后,应用免疫组织化学的方法分析肝再生过程中的PCNA阳性细胞率；采用HPLC技术检测肝脏内羟基胆固醇的变化；运用实时定量PCR和免疫印迹法检测基因表达水平。
结果：SULT2B1b过表达的小鼠肝脏恢复较快,约于术后三天恢复到肝脏原始大小的80%,而对照组需要将近5天达到同样水平。SULT2B1b过表达增加了肝脏再生过程中的PCNA阳性细胞率以及增生相关基因的表达水平；降低了肝脏内的羟基胆固醇含量以及LXR信号转导通路下游基因SREBP-1和ABCA1的表达水平。
结论：SULT2B1b能够通过抑制羟基胆固醇/LXR信号转导通路促进肝脏损伤后的再生。
第二部分在小鼠体内研究羟基胆固醇硫化物对肝脏增生的影响及其相关机制
目的：探索SULT2B1b的硫化产物(25HC3S)对小鼠体内肝脏增生的影响及机制
方法：向C57BL/6小鼠尾静脉直接注射3-硫酸-25-羟化胆固醇(25HC3S)化合物,或向感染了腺病毒(Ad-SULT2B1b)两天后的C57BL/6小鼠腹腔内注射25HC,建立高浓度外源性或内源性25HC3S的小鼠模型；应用[3H]标记25HC3S并经尾静脉注射小鼠体内,追踪25HC3S在各组织器官中的分布及其药代动力学：采用实时定量PCR,细胞周期PCR芯片以及免疫印迹法检测相关基因的表达水平。以PCNA为增生标记,应用免疫组织化学技术分析肝脏中PCNA的阳性细胞数。
结果：外源性25HC3S给药后在小鼠体内广泛分布于各组织器官,并在注射后48小时左右减至初始剂量的一半25HC3S的增加上调了肝脏内增生相关基因Wtl, Pcna,cMyc, cyclin A, FoxM1b, CDC25b的表达,却下调了细胞周期停滞基因Check2以及凋亡诱导基因Apafl的表达；无论外源性给药还是内源性合成,25HC3S的应用均有效增加了PCNA阳性细胞率,降低了LXR信号转导通路下游基因如ABCA1和SREBP-lc的表达；最后,LXR的人工合成激动剂T0901317的应用有效阻止了25HC3S诱导的PCNA表达升高。
结论：25HC3S能够促进肝脏增生。羟基胆固醇硫酸化通过对LXR信号转导通路的抑制为肝脏增生的研究提供了新的靶点。
综上所述,羟基类固醇硫酸基转移酶(SULT2B1b)通过硫酸化羟基胆固醇,增加硫化羟基胆固醇(25HC3S)的产生,抑制LXR信号转导通路活性,从而促进肝脏增生以及肝脏损伤后的再生恢复。
Introduction
Cytosolic sulfotransferase (SULT)2Blb catalyzes sulfation of oxysterol and hydroxysterol, including25-hydroxycholesterol (25HC). The main product of this reaction is25-hydroxycholesterol-3-sulfate (25HC3S). It has been reported that SULT2Blb inhibits the activation of oxysterol to Liver X Receptors (LXRs) and25HC3S decreases cellular lipids via suppressing LXR/sterol regulatory element-binding proteins (SREBPs) signaling in THP-1derived macrophages. Furthermore, LXR activation has been identified as anti-proliferative factor in several cellular and animal models. Therefore, the key enzyme for the biosynthesis of25HC3S, SULT2Blb, may play a crucial role in regulating liver proliferation. In the present study, we investigated the effects and mechanisms of SULT2B1b and its product-25HC3S in liver proliferation in mouse liver with or without partial hepatectomy (PH) and in primary rat hepatocyte (PRH).
Part Ⅰ. Effect of SULT2Blb on hepatic proliferation in vivo and in vitro
Section I:The effect and mechanism of cytosolic sulfotransferase2Blb (SULT2B1b) on proliferation in mouse liver tissues and in primary rat hepatocyte (PRH)
Aims:To investigate the effect and the underlying mechanism of SULT2Blb on liver proliferation in vivo and in vitro.
Methods:Primary rat hepatocyte (PRH) and C57BL/6mice were infected with adenovirus encoding SULT2B1b. Liver proliferation was determined by measuring the proliferating cell nuclear antigen (PCNA) immunostaining labeling index. The correlation between the SULT2B1b and PCNA expression in mouse liver tissues were determined by double immunofluorescence. Gene expressions were evaluated by quantitative real-time PCR and western blot analysis.
Results:SULT2B1b overexpression in mouse liver tissues increased PCNA-positive cells in a dose-and time-dependent manner. The expression of PCNA in mouse liver tissues was almost observed in the SULT2Blb-transgenic cells, while PCNA is undetectable in the cells without SULT2Blb overexpression. Small interference RNA-SULT2B1b significantly inhibited cell cycle regulatory gene expressions in primary rat hepatocytes (PRH). LXR activation by T0901317, effectively suppressed SULT2B1b-induced gene expression both in vivo and in vitro.
Conclusions:SULT2B1b may promote hepatocyte proliferation via inactivating oxysterol/LXR signaling in vivo and in vitro.
Section Ⅱ:Effect of SULT2Blb on liver regeneration following mouse partial hepatectomy (PH)
Aims:To evaluate the effect and mechanism of SULT2B11b on liver regeneration.
Methods:C57BL/6mice were performed PH and infected with Ad-SULT2B1b or Ad-control for5days. Liver proliferation was determined by measuring the PCNA immunostaining labeling index. Levels of hepatic oxysterols were analysed by HPLC. Gene expressions were evaluated by quantitative real-time PCR and western blot analysis.
Results:C57BL/6mice infected with Ad-SULT2Blb exhibited a faster liver re-growth, taking3days to reach80%of their original liver mass, while control mice took nearly5days to reach this liver mass. Following PH, SULT2B1b overexpression resulted in an apparent reduction of oxysterols coupled with a further down-regulation of the LXR signaling while the expression of proliferative genes were further increased. T0901317, a synthetic agonist of LXR, completely blocked SULT2B1b-induced increases in PCNA protein and decreases in the LXR signaling pathway.
Conclusions:Increases in SULT2B1b promote Liver regeneration after PH via inhibiting LXR signaling.
Part II. Effect of cholesterol metabolite (25HC3S) on hepatic proliferation in mice
Aims:To determine the effects of exogenous or endogenous25HC3S on the hepatic proliferation in vivo of C57BL/6mice.
Methods:C57BL/6mice were injected with exogenous25HC3S, or infected with adenovirus encoding SULT2B1b, combined by25HC administration to get endogenous25HC3S. The biodistribution of exogenous25HC3S in tissues and the formation of endogenous25HC3S in liver was examined by [3H]-25HC3S radioactivity analysis. Hepatic gene expressions were evaluated by quantitative real-time PCR, cell cycle RT2ProfilerTM PCR array, and western blot analysis. Liver proliferation was determined by measuring the proliferating cell nuclear antigen (PCNA) immunostaining labeling index (LI).
Results:Following exogenous administration,25HC3S had a48h half life in circulation and widely distributed in mouse tissues.25HC3S or overexpression of SULT2B1b plus administration of25HC (endogenous25HC3S) significantly up-regulated the proliferation gene expression of Wt1, Pcna, cMyc, cyclin A, FoxM1b, and CDC25b in a dose-dependent manner in liver; substantially down-regulated the expression of cell cycle arrest gene Chek2and apoptotic gene Apaf1. Both exogenous and endogenous administration of25HC3S significantly induced hepatic DNA replication as measured by immunostaining of the PCNA labeling index and associated with reduction in expression of LXRs response genes, such as ABCA1and SREBPlc. LXR activation by synthetic agonist T0901317effectively blocked the25HC3S-induced hepatic proliferation.
Conclusions:25HC3S is a potent regulator of proliferation and the oxysterol sulfation may represent a novel regulatory pathway in liver proliferation via inactivating LXR signaling.
In summary,25HC sulfation by SULT2B1b may promote hepatic proliferation and regeneration by down-regulation of LXR signaling pathway in vitro PRH and in vivo mouse liver tissues.
引文
[1]Coughtrie MW, Sharp S, Maxwell K, Innes NP. Biology and function of the reversible sulfation pathway catalysed by human sulfotransferases and sulfatases. Chem Biol Interact. 1998; 109:3-27.
[2]Falany CN. Enzymology of human cytosolic sulfotransferases. FASEB J.1997;11:206-16.
[3]Strott CA. Sulfonation and molecular action. Endocr Rev.2002;23:703-32.
[4]Nagata K, Yamazoe Y. Pharmacogenetics of sulfotransferase. Annu Rev Pharmacol Toxicol. 2000;40:159-76.
[5]Her C, Wood TC, Eichler EE, Mohrenweiser HW, Ramagli LS, Siciliano MJ, et al. Human hydroxysteroid sulfotransferase SULT2B1:two enzymes encoded by a single chromosome 19 gene. Genomics.1998;53:284-95.
[6]He D, Meloche CA, Dumas NA, Frost AR, Falany CN. Different subcellular localization of sulphotransferase 2B1b in human placenta and prostate. Biochem J.2004;379:533-40.
[7]Falany CN, He D, Dumas N, Frost AR, Falany JL. Human cytosolic sulfotransferase 2B1: isoform expression, tissue specificity and subcellular localization. J Steroid Biochem Mol Biol.2006; 102:214-21.
[8]Higashi Y, Fuda H, Yanai H, Lee Y, Fukushige T, Kanzaki T, et al. Expression of cholesterol sulfotransferase (SULT2B1b) in human skin and primary cultures of human epidermal keratinocytes. J Invest Dermatol.2004; 122:1207-13.
[9]He D, Frost AR, Falany CN. Identification and immunohistochemical localization of Sulfotransferase 2B1b (SULT2B1b) in human lung. Biochim Biophys Acta. 2005; 1724:119-26.
[10]Yanai H, Javitt NB, Higashi Y, Fuda H, Strott CA. Expression of cholesterol sulfotransferase (SULT2B1b) in human platelets. Circulation.2004; 109:92-6.
[11]Meinl W, Ebert B, Glatt H, Lampen A. Sulfotransferase forms expressed in human intestinal Caco-2 and TC7 cells at varying stages of differentiation and role in benzo[a]pyrene metabolism. Drug Metab Dispos.2008;36:276-83.
[12]Li X, Pandak WM, Erickson SK, Ma Y, Yin L, Hylemon P, et al. Biosynthesis of the regulatory oxysterol,5-cholesten-3beta,25-diol 3-sulfate, in hepatocytes. J Lipid Res. 2007;48:2587-96.
[13]Fuda H, Lee YC, Shimizu C, Javitt NB, Strott CA. Mutational analysis of human hydroxysteroid sulfotransferase SULT2B1 isoforms reveals that exon 1B of the SULT2B1 gene produces cholesterol sulfotransferase, whereas exon 1A yields pregnenolone sulfotransferase. J Biol Chem.2002;277:36161-6.
[14]Meloche CA, Falany CN. Expression and characterization of the human 3 beta-hydroxysteroid sulfotransferases (SULT2B1a and SULT2B1b). J Steroid Biochem Mol Biol. 2001;77:261-9.
[15]Fuda H, Javitt NB, Mitamura K, Ikegawa S, Strott CA. Oxysterols are substrates for cholesterol sulfotransferase. J Lipid Res.2007;48:1343-52.
[16]Cook IT, Duniec-Dmuchowski Z, Kocarek TA, Runge-Morris M, Falany CN.24-hydroxycholesterol sulfation by human cytosolic sulfotransferases:formation of monosulfates and disulfates, molecular modeling, sulfatase sensitivity, and inhibition of liver x receptor activation. Drug Metab Dispos.2009;37:2069-78.
[17]Bai Q, Xu L, Kakiyama G, Runge-Morris MA, Hylemon PB, Yin L, et al. Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-lc signaling pathway in human aortic endothelial cells. Atherosclerosis.2011;214:350-6.
[18]Bjorkhem I. Do oxysterols control cholesterol homeostasis? J Clin Invest.2002; 110:725-30.
[19]Chen W, Chen G, Head DL, Mangelsdorf DJ, Russell DW. Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab. 2007;5:73-9.
[20]Nomiyama T, Bruemmer D. Liver X receptors as therapeutic targets in metabolism and atherosclerosis. Curr Atheroscler Rep.2008; 10:88-95.
[21]Liang G, Yang J, Horton JD, Hammer RE, Goldstein JL, Brown MS. Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-lc. J Biol Chem.2002;277:9520-8.
[22]Chen G, Liang G, Ou J, Goldstein JL, Brown MS. Central role for liver X receptor in insulin-mediated activation of Srebp-lc transcription and stimulation of fatty acid synthesis in liver. Proc Natl Acad Sci U S A,2004; 101:11245-50.
[23]Talukdar S, Hillgartner FB. The mechanism mediating the activation of acetyl-coenzyme A carboxylase-alpha gene transcription by the liver X receptor agonist TO-901317. J Lipid Res. 2006;47:2451-61.
[24]Joseph SB, Laffitte BA, Patel PH, Watson MA, Matsukuma KE, Walczak R, et al. Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. J Biol Chem.2002;277:11019-25.
[25]Ren S, Li X, Rodriguez-Agudo D, Gil G, Hylemon P, Pandak WM. Sulfated oxysterol, 25HC3S, is a potent regulator of lipid metabolism in human hepatocytes. Biochem Biophys Res Commun.2007;360:802-8.
[26]Ma Y, Xu L, Rodriguez-Agudo D, Li X, Heuman DM, Hylemon PB, et al.25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. Am J Physiol Endocrinol Metab.2008;295:E 1369-79.
[27]Bensinger SJ, Bradley MN, Joseph SB, Zelcer N, Janssen EM, Hausner MA, et al. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell. 2008;134:97-111.
[28]Blaschke F, Leppanen O, Takata Y, Caglayan E, Liu J, Fishbein MC, et al. Liver X receptor agonists suppress vascular smooth muscle cell proliferation and inhibit neointima formation in balloon-injured rat carotid arteries. Circ Res.2004;95:e110-23.
[29]Vedin LL, Lewandowski SA, Parini P, Gustafsson JA, Steffensen KR. The oxysterol receptor LXR inhibits proliferation of human breast cancer cells. Carcinogenesis. 2009;30:575-9.
[30]Lo Sasso G, Celli N, Caboni M, Murzilli S, Salvatore L, Morgano A, et al. Down-regulation of the LXR transcriptome provides the requisite cholesterol levels to proliferating hepatocytes. Hepatology.2010;51:1334-44.
[31]Fukuchi J, Kokontis JM, Hiipakka RA, Chuu CP, Liao S. Antiproliferative effect of liver X receptor agonists on LNCaP human prostate cancer cells. Cancer Res.2004;64:7686-9.
[32]Chuu CP, Hiipakka RA, Fukuchi J, Kokontis JM, Liao S. Androgen causes growth suppression and reversion of androgen-independent prostate cancer xenografts to an androgen-stimulated phenotype in athymic mice. Cancer Res.2005;65:2082-4.
[33]Chuu CP, Chen RY, Hiipakka RA, Kokontis JM, Warner KV, Xiang J, et al. The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells. Biochem Biophys Res Commun.2007;357:341-6.
[34]Hylemon PB, Gurley EC, Stravitz RT, Litz JS, Pandak WM, Chiang JY, et al. Hormonal regulation of cholesterol 7 alpha-hydroxylase mRNA levels and transcriptional activity in primary rat hepatocyte cultures. J Biol Chem.1992;267:16866-71.
[35]Ren S, Hylemon P, Marques D, Hall E, Redford K, Gil G, et al. Effect of increasing the expression of cholesterol transporters (StAR, MLN64, and SCP-2) on bile acid synthesis. J Lipid Res.2004;45:2123-31.
[36]Olle EW, Ren X, McClintock SD, Warner RL, Deogracias MP, Johnson KJ, et al. Matrix metalloproteinase-9 is an important factor in hepatic regeneration after partial hepatectomy in mice. Hepatology.2006;44:540-9.
[37]Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature.1996;383:728-31.
[38]Vidyashankar S, Varma SR, Azeemudin M, Godavarthi A, Krishna NS, Patki PS. A Novel Herbal Formulation "LiverCare" Differentially Regulates Primary Rat Hepatocyte and Hepatocarcinoma Cell Proliferation In Vitro. J Med Food.2011; 14:1023-31.
[39]Shimizu C, Fuda H, Yanai H, Strott CA. Conservation of the hydroxysteroid sulfotransferase SULT2B1 gene structure in the mouse:pre- and postnatal expression, kinetic analysis of isoforms, and comparison with prototypical SULT2A1. Endocrinology. 2003;144:1186-93.
[40]Hanley K, Wood L, Ng DC, He SS, Lau P, Moser A, et al. Cholesterol sulfate stimulates involucrin transcription in keratinocytes by increasing Fra-1, Fra-2, and Jun D. J Lipid Res. 2001;42:390-8.
[41]Zhang B, Cheng Q, Ou Z, Lee JH, Xu M, Kochhar U, et al. Pregnane X receptor as a therapeutic target to inhibit androgen activity. Endocrinology.2010; 151:5721-9.
[42]Chen Y, Chen X, Zhang S, Chen G. Influenza A virus infection activates cholesterol sulfotransferase (SULT2B1b) in the lung of female C57BL/6 mice. Biol Chem. 2011;392:869-76.
[43]Lees E, Faha B, Dulic V, Reed SI, Harlow E. Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with p107 and E2F in a temporally distinct manner. Genes Dev.1992;6:1874-85.
[44]Wang X, Krupczak-Hollis K, Tan Y, Dennewitz MB, Adami GR, Costa RH. Increased hepatic Forkhead Box M1B (FoxM1B) levels in old-aged mice stimulated liver regeneration through diminished p27Kip1 protein levels and increased Cdc25B expression. J Biol Chem. 2002;277:44310-6.
[45]Hanse EA, Nelsen CJ, Goggin MM, Anttila CK, Mullany LK, Berthet C, et al. Cdk2 plays a critical role in hepatocyte cell cycle progression and survival in the setting of cyclin Dl expression in vivo. Cell Cycle.2009;8:2802-9.
[46]Kim KH, Lee GY, Kim JI, Ham M, Won Lee J, Kim JB. Inhibitory effect of LXR activation on cell proliferation and cell cycle progression through lipogenic activity. J Lipid Res. 2010;51:3425-33.
[47]Choe SS, Choi AH, Lee JW, Kim KH, Chung JJ, Park J, et al. Chronic activation of liver X receptor induces beta-cell apoptosis through hyperactivation of lipogenesis:liver X receptor-mediated lipotoxicity in pancreatic beta-cells. Diabetes.2007;56:1534-43.
[48]Javitt NB, Lee YC, Shimizu C, Fuda H, Strott CA. Cholesterol and hydroxycholesterol sulfotransferases:identification, distinction from dehydroepiandrosterone sulfotransferase, and differential tissue expression. Endocrinology.2001; 142:2978-84.
[49]O'Callaghan YC, Woods JA, O'Brien NM. Oxysterol-induced cell death in U937 and HepG2 cells at reduced and normal serum concentrations. Eur J Nutr.1999;38:255-62.
[50]Bochelen D, Mersel M, Behr P, Lutz P, Kupferberg A. Effect of oxysterol treatment on cholesterol biosynthesis and reactive astrocyte proliferation in injured rat brain cortex. J Neurochem.1995:65:2194-200.
1. Michalopoulos, G. K., and M. C. DeFrances.1997. Liver regeneration. Science 276:60-66.
2. Fausto, N., J. S. Campbell, and K. J. Riehle.2006. Liver regeneration. Hepatology 43:S45-53.
3. Karp, S. J.2009. Clinical implications of advances in the basic science of liver repair and regeneration. Am J Transplant 9:1973-1980.
4. Michalopoulos, G. K.2010. Liver regeneration after partial hepatectomy:critical analysis of mechanistic dilemmas. Am JPathol 176:2-13.
5. Makino, H., H. Shimizu, H. Ito, F. Kimura, S. Ambiru, A. Togawa, M. Ohtsuka, H. Yoshidome, A. Kato, H. Yoshitomi, S. Sawada, and M. Miyazaki.2006. Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy. World J Gastroenterol 12:2053-2059.
6. Bensinger, S. J., M. N. Bradley, S. B. Joseph, N. Zelcer, E. M. Janssen, M. A. Hausner, R. Shih, J. S. Parks, P. A. Edwards, B. D. Jamieson, and P. Tontonoz.2008. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell 134:97-111.
7. Blaschke, F., O. Leppanen, Y. Takata, E. Caglayan, J. Liu, M. C. Fishbein, K. Kappert, K. I. Nakayama, A. R. Collins, E. Fleck, W. A. Hsueh, R. E. Law, and D. Bruemmer.2004. Liver X receptor agonists suppress vascular smooth muscle cell proliferation and inhibit neointima formation in balloon-injured rat carotid arteries. Circ Res 95:e110-123.
8. Vedin, L. L., S. A. Lewandowski, P. Parini, J. A. Gustafsson, and K. R. Steffensen.2009. The oxysterol receptor LXR inhibits proliferation of human breast cancer cells. Carcinogenesis 30:575-579.
9. Lo Sasso, G., N. Celli, M. Caboni, S. Murzilli, L. Salvatore, A. Morgano, M. Vacca, T. Pagliani, P. Parini, and A. Moschetta.2010. Down-regulation of the LXR transcriptome provides the requisite cholesterol levels to proliferating hepatocytes. Hepatology 51:1334-1344.
10. Fukuchi, J., R. A. Hiipakka, J. M. Kokontis, S. Hsu, A. L. Ko, M. L. Fitzgerald, and S. Liao. 2004. Androgenic suppression of ATP-binding cassette transporter Al expression in LNCaP human prostate cancer cells. Cancer Res 64:7682-7685.
11. Chuu, C. P., R. A. Hiipakka, J. Fukuchi, J. M. Kokontis, and S. Liao.2005. Androgen causes growth suppression and reversion of androgen-independent prostate cancer xenografts to an androgen-stimulated phenotype in athymic mice. Cancer Res 65:2082-2084.
12. Nomiyama, T., and D. Bruemmer,2008. Liver X receptors as therapeutic targets in metabolism and atherosclerosis. Curr Atheroscler Rep 10:88-95.
13. Cook, I. T., Z. Duniec-Dmuchowski, T. A. Kocarek, M. Runge-Morris, and C. N. Falany. 2009.24-hydroxycholesterol sulfation by human cytosolic sulfotransferases:formation of monosulfates and disulfates, molecular modeling, sulfatase sensitivity, and inhibition of liver x receptor activation. Drug Me tab Dispos 37:2069-2078.
14. Bai, Q., L. Xu, G. Kakiyama, M. A. Runge-Morris, P. B. Hylemon, L. Yin, W. M. Pandak, and S. Ren.2011. Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-lc signaling pathway in human aortic endothelial cells. Atherosclerosis 214:350-356.
15. Bjorkhem, I.2002. Do oxysterols control cholesterol homeostasis? J Clin Invest 110:725-730.
16. Chen, W., G. Chen, D. L. Head, D. J. Mangelsdorf, and D. W. Russell 2007. Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab 5:73-79.
17. Zhang, Z., D. Li, D. E. Blanchard, S. R. Lear, S. K. Erickson, and T. A. Spencer.2001. Key regulatory oxysterols in liver:analysis as delta4-3-ketone derivatives by HPLC and response to physiological perturbations. J Lipid Res 42:649-658.
18. Taub, R.2004. Liver regeneration:from myth to mechanism. Nat Rev Mol Cell Biol 5:836-847.
19. Locker, J., J. Tian, R. Carver, D. Concas, C. Cossu, G. M. Ledda-Columbano, and A. Columbano.2003. A common set of immediate-early response genes in liver regeneration and hyperplasia. Hepatology 38:314-325.
20. Xu, L., Q. Bai, D. Rodriguez-Agudo, P. B. Hylemon, D. M. Heuman, W. M. Pandak, and S. Ren.2010. Regulation of hepatocyte lipid metabolism and inflammatory response by 25-hydroxycholesterol and 25-hydroxycholesterol-3-sulfate. Lipids 45:821-832.
21. Xu, L., S. Shen, Y. Ma, J. K. Kim, D. Rodriguez-Agudo, D. M. Heuman, P. B. Hylemon, W. M. Pandak, and S. Ren.2012.25-Hydroxycholesterol-3-Sulfate (25HC3S) Attenuates Inflammatory Response via PPARgamma Signaling in Human THP-1 Macrophages. Am J Physiol Endocrinol Metab.
22. Schroepfer, G. J., Jr.2000. Oxysterols:modulators of cholesterol metabolism and other processes. Physiol Rev 80:361-554.
23. Ma, Y., L. Xu, D. Rodriguez-Agudo, X. Li, D. M. Heuman, P. B. Hylemon, W. M. Pandak, and S. Ren.2008.25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-I signaling pathway. Am J Physiol Endocrinol Metab 295:E1369-1379.
1. Vlahcevic, Z. R., W. M. Pandak, and R. T. Stravitz.1999. Regulation of bile acid biosynthesis. Gastroenterol Clin North Am 28:1-25, v.
2. Pandak, W. M., D. M. Heuman, P. B. Hylemon, and Z. R. Vlahcevic.1990. Regulation of bile acid synthesis. IV. Interrelationship between cholesterol and bile acid biosynthesis pathways. J Lipid Res 31:79-90.
3. Chiang, J. Y.2003. Bile acid regulation of hepatic physiology. Ⅲ. Bile acids and nuclear receptors. Am J Physiol Gastrointest Liver Physiol 284:G349-356.
4. Hylemon, P. B., R. T. Stravitz, and Z. R. Vlahcevic.1994. Molecular genetics and regulation of bile acid biosynthesis. Prog Liver Dis 12:99-120.
5. Goodwin, B., M. A. Watson, H. Kim, J. Miao, J. K. Kemper, and S. A. Kliewer.2003. Differential regulation of rat and human CYP7A1 by the nuclear oxysterol receptor liver X receptor-alpha. Mol Endocrinol 17:386-394.
6. Fu, X., J. G. Menke, Y. Chen, G. Zhou, K. L. MacNaul, S. D. Wright, C. P. Sparrow, and E. G. Lund.2001,27-hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells. J Biol Chem 276:38378-38387.
7. Javitt, N. B.2002. Cholesterol, hydroxycholesterols, and bile acids. Biochem Biophys Res Commun 292:1147-1153.
8. Meir, K., D. Kitsberg, I. Alkalay, F. Szafer, H. Rosen, S. Shpitzen, L. B. Avi, B. Staels, C. Fievet, V. Meiner, I. Bjorkhem, and E. Leitersdorf.2002. Human sterol 27-hydroxylase (CYP27) overexpressor transgenic mouse model. Evidence against 27-hydroxycholesterol as a critical regulator of cholesterol homeostasis. J Biol Chem 111:34036-34041.
9. O'Callaghan, Y. C., J. A. Woods, and N. M. O'Brien.1999. Oxysterol-induced cell death in U937 and HepG2 cells at reduced and normal serum concentrations. Eur J Nutr 38:255-262.
10. Corsini, A., D. Verri, M. Raiteri, P. Quarato, R. Paoletti, and R. Fumagalli.1995. Effects of 26-aminocholesterol,27-hydroxycholesterol, and 25-hydroxycholesterol on proliferation and cholesterol homeostasis in arterial myocytes. Arterioscler Thromb Vasc Biol 15:420-428.
11. Meng, Z., N. Liu, X. Fu, X. Wang, Y. D. Wang, W. D. Chen, L. Zhang, B. M. Forman, and W. Huang.2011. Insufficient bile acid signaling impairs liver repair in CYP27(-/-) mice. J Hepatol 55:885-895.
12. Ren, S., P. Hylemon, Z. P. Zhang, D. Rodriguez-Agudo, D. Marques, X. Li, H. Zhou, G. Gil, and W. M. Pandak.2006. Identification of a novel sulfonated oxysterol,5-cholesten-3beta,25-diol 3-sulfonate, in hepatocyte nuclei and mitochondria. J Lipid Res 47:1081-1090.
13. Pandak, W. M., S. Ren, D. Marques, E. Hall, K. Redford, D. Mallonee, P. Bohdan, D. Heuman, G. Gil, and P. Hylemon.2002. Transport of cholesterol into mitochondria is rate-limiting for bile acid synthesis via the alternative pathway in primary rat hepatocytes. J Biol Chem 277:48158-48164.
14. Ren, S., P. Hylemon, D. Marques, E. Hall, K. Redford, G. Gil, and W. M. Pandak.2004. Effect of increasing the expression of cholesterol transporters (StAR, MLN64, and SCP-2) on bile acid synthesis. J Lipid Res 45:2123-2131.
15. Li, X., W. M. Pandak, S. K. Erickson, Y. Ma, L. Yin, P. Hylemon, and S. Ren.2007. Biosynthesis of the regulatory oxysterol,5-cholesten-3beta,25-diol 3-sulfate, in hepatocytes. J Lipid Res 48:2587-2596.
16. Ma, Y., L. Xu, D. Rodriguez-Agudo, X. Li, D. M. Heuman, P. B. Hylemon, W. M. Pandak, and S. Ren.2008.25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. Am J Physiol Endocrinol Metab 295:E1369-1379.
17. Lo Sasso, G., N. Celli, M. Caboni, S. Murzilli, L. Salvatore, A. Morgano, M. Vacca, T. Pagliani, P. Parini, and A. Moschetta.2010. Down-regulation of the LXR transcriptome provides the requisite cholesterol levels to proliferating hepatocytes. Hepatology 51:1334-1344.
18. Bensinger, S. J., M. N. Bradley, S. B. Joseph, N. Zelcer, E. M. Janssen, M. A. Hausner, R. Shih, J. S. Parks, P. A. Edwards, B. D. Jamieson, and P. Tontonoz.2008. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell 134:97-111.
19. Blaschke, F., O. Leppanen, Y. Takata, E. Caglayan, J. Liu, M. C. Fishbein, K. Kappert, K. I. Nakayama, A. R. Collins, E. Fleck, W. A. Hsueh, R. E. Law, and D. Bruemmer.2004. Liver X receptor agonists suppress vascular smooth muscle cell proliferation and inhibit neointima formation in balloon-injured rat carotid arteries. Circ Res 95:e110-123.
20. Vedin, L. L., S. A. Lewandowski, P. Parini, J. A. Gustafsson, and K. R. Steffensen.2009. The oxysterol receptor LXR inhibits proliferation of human breast cancer cells. Carcinogenesis 30:575-579.
21. Kim, K. H., G. Y. Lee, J. I. Kim, M. Ham, J. Won Lee, and J. B. Kim.2010. Inhibitory effect of LXR activation on cell proliferation and cell cycle progression through lipogenic activity. J Lipid Res 51:3425-3433.
22. Fukuchi, J., J. M. Kokontis, R. A. Hiipakka, C. P. Chuu, and S. Liao.2004. Antiproliferative effect of liver X receptor agonists on LNCaP human prostate cancer cells. Cancer Res 64:7686-7689.
23. Ren, S., X. Li, D. Rodriguez-Agudo, G. Gil, P. Hylemon, and W. M. Pandak.2007. Sulfated oxysterol,25HC3S, is a potent regulator of lipid metabolism in human hepatocytes. Biochem Biophys Res Commun 360:802-808.
24. Qianming Bai, X. Z., Leyuan Xu, Genta Kakiyama, Douglas Heuman, Arun Sanyal, William M. Pandak, Lianhua Yin, Wen Xie, Shunlin Ren. Oxysterol sulfation by cytosolic sulfotranseferase suppresses liver X receptor/sterol regulatory element binding protein-lc signaling pathway and reduces serum and hepatic lipids in mouse models of nonalcohol fatty liver disease. Metabolism.
25. Wang, X., K. Krupczak-Hollis, Y. Tan, M. B. Dennewitz, G. R. Adami, and R. H. Costa. 2002. Increased hepatic Forkhead Box M1B (FoxM1B) levels in old-aged mice stimulated liver regeneration through diminished p27Kipl protein levels and increased Cdc25B expression. J Biol Chem 111:44310-44316.
26. Huff, V.2011. Wilms'tumours:about tumour suppressor genes, an oncogene and a chameleon gene. Nat Rev Cancer 11:111-121.
27. Kelman, Z.1997. PCNA:structure, functions and interactions. Oncogene 14:629-640.
28. Harbour, J. W., and D. C. Dean.2000. The Rb/E2F pathway:expanding roles and emerging paradigms. Genes Dev 14:2393-2409.
29. Zachariae, W., and K. Nasmyth.1999. Whose end is destruction:cell division and the anaphase-promoting complex. Genes Dev 13:2039-2058.
30. Matsuoka, S., M. Huang, and S. J. Elledge.1998. Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 282:1893-1897.
31. Cain, K.2003. Chemical-induced apoptosis:formation of the Apaf-1 apoptosome. Drug Metab Rev 35:337-363.
32. Li, X., P. Hylemon, W. M. Pandak, and S. Ren.2006. Enzyme activity assay for cholesterol 27-hydroxylase in mitochondria. J Lipid Res 47:1507-1512.
33. Xu, L., Q. Bai, D. Rodriguez-Agudo, P. B. Hylemon, D. M. Heuman, W. M. Pandak, and S. Ren.2010. Regulation of hepatocyte lipid metabolism and inflammatory response by 25-hydroxycholesterol and 25-hydroxycholesterol-3-sulfate. Lipids 45:821-832.
34. Bai, Q., L. Xu, G. Kakiyama, M. A. Runge-Morris, P. B. Hylemon, L. Yin, W. M. Pandak, and S. Ren.2011. Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-lc signaling pathway in human aortic endothelial cells. Atherosclerosis 214; 350-356.
35. Nilsson,1., and I. Hoffmann.2000. Cell cycle regulation by the Cdc25 phosphatase family. Prog Cell Cycle Res 4:107-114.
36. Sebastian, B., A. Kakizuka, and T. Hunter.1993. Cdc25M2 activation of cyclin-dependent kinases by dephosphorylation of threonine-14 and tyrosine-15. Proc Natl A cad Sci USA 90: 3521-3524.
37. Trembley, J. H., J. O. Ebbert, B. T. Kren, and C. J. Steer.1996. Differential regulation of cyclin B1 RNA and protein expression during hepatocyte growth in vivo. Cell Growth Differ 7:903-916.
38. Sohn, V. R., A. Giros, R. M. Xicola, L. Fluvia, M. Grzybowski, A. Anguera, and X. Llor. 2011. Stool-fermented Plantago ovata husk induces apoptosis in colorectal cancer cells independently of molecular phenotype. Br J Nutr:1-12.
39. Petry, I. B., E. Fieber, M. Schmidt, M. Gehrmann, S. Gebhard, M. Hermes, W. Schormann, S. Selinski, E. Freis, H. Schwender, M. Brulport, K. Ickstadt, J. Rahnenfuhrer, L. Maccoux, J. West, H. Kolbl, M. Schuler, and J. G. Hengstler.2010. ERBB2 induces an antiapoptotic expression pattern of Bcl-2 family members in node-negative breast cancer. Clin Cancer Res 16:451-460.
40. Vedin, I., T. Cederholm, Y. Freund-Levi, H. Basun, E. Hjorth, G. F. Irving, M. Eriksdotter-Jonhagen, M. Schultzberg, L. O. Wahlund, and J. Palmblad.2010. Reduced prostaglandin F2 alpha release from blood mononuclear leukocytes after oral supplementation of omega3 fatty acids:the OmegAD study. J Lipid Res 51:1179-1185.
41. Coughtrie, M. W., S. Sharp, K. Maxwell, and N. P. Innes.1998. Biology and function of the reversible sulfation pathway catalysed by human sulfotransferases and sulfatases. Chem Biol Interact 109:3-27.
42. Falany, C. N.1997. Enzymology of human cytosolic sulfotransferases. FASEB J 11:206-216.
43. Strott, C. A.2002. Sulfonation and molecular action. Endocr Rev 23:703-732.
44. Falany, C. N., D. He, N. Dumas, A. R. Frost, and J. L. Falany.2006. Human cytosolic sulfotransferase 2B1:isoform expression, tissue specificity and subcellular localization. J Steroid Biochem Mol Biol 102:214-221.
45. He, D., A. R. Frost, and C. N. Falany.2005. Identification and immunohistochemical localization of Sulfotransferase 2B1b (SULT2B1b) in human lung. Biochim Biophys Acta 1724:119-126.
46. He, D., C. A. Meloche, N. A. Dumas, A. R. Frost, and C. N. Falany.2004. Different subcellular localization of sulphotransferase 2B1b in human placenta and prostate. Biochem J 379:533-540.
47. Higashi, Y., H. Fuda, H. Yanai, Y. Lee, T. Fukushige, T. Kanzaki, and C. A. Strott.2004. Expression of cholesterol sulfotransferase (SULT2B1b) in human skin and primary cultures of human epidermal keratinocytes. J Invest Dermatol 122:1207-1213.
48. Meinl, W., B. Ebert, H. Glatt, and A. Lampen.2008. Sulfotransferase forms expressed in human intestinal Caco-2 and TC7 cells at varying stages of differentiation and role in benzo[a]pyrene metabolism. Drug Me tab Dispos 36:276-283.
49. Yanai, H., N. B. Javitt, Y. Higashi, H. Fuda, and C. A. Strott.2004. Expression of cholesterol sulfotransferase (SULT2B1b) in human platelets. Circulation 109:92-96.
50. Fuda, H., Y. C. Lee, C. Shimizu, N. B. Javitt, and C. A. Strott.2002. Mutational analysis of human hydroxysteroid sulfotransferase SULT2B1 isoforms reveals that exon 1B of the SULT2B1 gene produces cholesterol sulfotransferase, whereas exon 1A yields pregnenolone sulfotransferase. J Biol Chem 277:36161-36166.
51. Meloche, C. A., and C. N. Falany.2001. Expression and characterization of the human 3 beta-hydroxysteroid sulfotransferases (SULT2B1a and SULT2B1b). J Steroid Biochem Mol Biol 77:261-269.
52. Fuda, H., N. B. Javitt, K. Mitamura, S. Ikegawa, and C. A. Strott.2007. Oxysterols are substrates for cholesterol sulfotransferase. JLipid Res 48:1343-1352.
53. Cook, I. T., Z. Duniec-Dmuchowski, T. A. Kocarek, M. Runge-Morris, and C. N. Falany. 2009.24-hydroxycholesterol sulfation by human cytosolic sulfotransferases:formation of monosulfates and disulfates, molecular modeling, sulfatase sensitivity, and inhibition of liver x receptor activation. Drug Metab Dispos 37:2069-2078.
54. Chen, W., G. Chen, D. L. Head, D. J. Mangelsdorf, and D. W. Russell.2007. Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab 5:73-79.
55. Schroepfer, G. J., Jr.2000. Oxysterols:modulators of cholesterol metabolism and other processes. Physiol Rev 80:361-554.
56. Snyder, V. L., M. Turner, P. K. Li, A. El-Sharkawy, G. Dunphy, and D. L. Ely.2000. Tissue steroid sulfatase levels, testosterone and blood pressure. J Steroid Biochem Mol Biol 73:251-256.
[2]Falany CN. Enzymology of human cytosolic sulfotransferases. FASEB J.1997;11:206-16.
[3]Strott CA. Sulfonation and molecular action. Endocr Rev.2002;23:703-32.
[4]Nagata K, Yamazoe Y. Pharmacogenetics of sulfotransferase. Annu Rev Pharmacol Toxicol. 2000;40:159-76.
[5]Her C, Wood TC, Eichler EE, Mohrenweiser HW, Ramagli LS, Siciliano MJ, et al. Human hydroxysteroid sulfotransferase SULT2B1:two enzymes encoded by a single chromosome 19 gene. Genomics.1998;53:284-95.
[6]He D, Meloche CA, Dumas NA, Frost AR, Falany CN. Different subcellular localization of sulphotransferase 2B1b in human placenta and prostate. Biochem J.2004;379:533-40.
[7]Falany CN, He D, Dumas N, Frost AR, Falany JL. Human cytosolic sulfotransferase 2B1: isoform expression, tissue specificity and subcellular localization. J Steroid Biochem Mol Biol.2006; 102:214-21.
[8]Higashi Y, Fuda H, Yanai H, Lee Y, Fukushige T, Kanzaki T, et al. Expression of cholesterol sulfotransferase (SULT2B1b) in human skin and primary cultures of human epidermal keratinocytes. J Invest Dermatol.2004; 122:1207-13.
[9]He D, Frost AR, Falany CN. Identification and immunohistochemical localization of Sulfotransferase 2B1b (SULT2B1b) in human lung. Biochim Biophys Acta. 2005; 1724:119-26.
[10]Yanai H, Javitt NB, Higashi Y, Fuda H, Strott CA. Expression of cholesterol sulfotransferase (SULT2B1b) in human platelets. Circulation.2004; 109:92-6.
[11]Meinl W, Ebert B, Glatt H, Lampen A. Sulfotransferase forms expressed in human intestinal Caco-2 and TC7 cells at varying stages of differentiation and role in benzo[a]pyrene metabolism. Drug Metab Dispos.2008;36:276-83.
[12]Li X, Pandak WM, Erickson SK, Ma Y, Yin L, Hylemon P, et al. Biosynthesis of the regulatory oxysterol,5-cholesten-3beta,25-diol 3-sulfate, in hepatocytes. J Lipid Res. 2007;48:2587-96.
[13]Fuda H, Lee YC, Shimizu C, Javitt NB, Strott CA. Mutational analysis of human hydroxysteroid sulfotransferase SULT2B1 isoforms reveals that exon 1B of the SULT2B1 gene produces cholesterol sulfotransferase, whereas exon 1A yields pregnenolone sulfotransferase. J Biol Chem.2002;277:36161-6.
[14]Meloche CA, Falany CN. Expression and characterization of the human 3 beta-hydroxysteroid sulfotransferases (SULT2B1a and SULT2B1b). J Steroid Biochem Mol Biol. 2001;77:261-9.
[15]Fuda H, Javitt NB, Mitamura K, Ikegawa S, Strott CA. Oxysterols are substrates for cholesterol sulfotransferase. J Lipid Res.2007;48:1343-52.
[16]Cook IT, Duniec-Dmuchowski Z, Kocarek TA, Runge-Morris M, Falany CN.24-hydroxycholesterol sulfation by human cytosolic sulfotransferases:formation of monosulfates and disulfates, molecular modeling, sulfatase sensitivity, and inhibition of liver x receptor activation. Drug Metab Dispos.2009;37:2069-78.
[17]Bai Q, Xu L, Kakiyama G, Runge-Morris MA, Hylemon PB, Yin L, et al. Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-lc signaling pathway in human aortic endothelial cells. Atherosclerosis.2011;214:350-6.
[18]Bjorkhem I. Do oxysterols control cholesterol homeostasis? J Clin Invest.2002; 110:725-30.
[19]Chen W, Chen G, Head DL, Mangelsdorf DJ, Russell DW. Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab. 2007;5:73-9.
[20]Nomiyama T, Bruemmer D. Liver X receptors as therapeutic targets in metabolism and atherosclerosis. Curr Atheroscler Rep.2008; 10:88-95.
[21]Liang G, Yang J, Horton JD, Hammer RE, Goldstein JL, Brown MS. Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-lc. J Biol Chem.2002;277:9520-8.
[22]Chen G, Liang G, Ou J, Goldstein JL, Brown MS. Central role for liver X receptor in insulin-mediated activation of Srebp-lc transcription and stimulation of fatty acid synthesis in liver. Proc Natl Acad Sci U S A,2004; 101:11245-50.
[23]Talukdar S, Hillgartner FB. The mechanism mediating the activation of acetyl-coenzyme A carboxylase-alpha gene transcription by the liver X receptor agonist TO-901317. J Lipid Res. 2006;47:2451-61.
[24]Joseph SB, Laffitte BA, Patel PH, Watson MA, Matsukuma KE, Walczak R, et al. Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. J Biol Chem.2002;277:11019-25.
[25]Ren S, Li X, Rodriguez-Agudo D, Gil G, Hylemon P, Pandak WM. Sulfated oxysterol, 25HC3S, is a potent regulator of lipid metabolism in human hepatocytes. Biochem Biophys Res Commun.2007;360:802-8.
[26]Ma Y, Xu L, Rodriguez-Agudo D, Li X, Heuman DM, Hylemon PB, et al.25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. Am J Physiol Endocrinol Metab.2008;295:E 1369-79.
[27]Bensinger SJ, Bradley MN, Joseph SB, Zelcer N, Janssen EM, Hausner MA, et al. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell. 2008;134:97-111.
[28]Blaschke F, Leppanen O, Takata Y, Caglayan E, Liu J, Fishbein MC, et al. Liver X receptor agonists suppress vascular smooth muscle cell proliferation and inhibit neointima formation in balloon-injured rat carotid arteries. Circ Res.2004;95:e110-23.
[29]Vedin LL, Lewandowski SA, Parini P, Gustafsson JA, Steffensen KR. The oxysterol receptor LXR inhibits proliferation of human breast cancer cells. Carcinogenesis. 2009;30:575-9.
[30]Lo Sasso G, Celli N, Caboni M, Murzilli S, Salvatore L, Morgano A, et al. Down-regulation of the LXR transcriptome provides the requisite cholesterol levels to proliferating hepatocytes. Hepatology.2010;51:1334-44.
[31]Fukuchi J, Kokontis JM, Hiipakka RA, Chuu CP, Liao S. Antiproliferative effect of liver X receptor agonists on LNCaP human prostate cancer cells. Cancer Res.2004;64:7686-9.
[32]Chuu CP, Hiipakka RA, Fukuchi J, Kokontis JM, Liao S. Androgen causes growth suppression and reversion of androgen-independent prostate cancer xenografts to an androgen-stimulated phenotype in athymic mice. Cancer Res.2005;65:2082-4.
[33]Chuu CP, Chen RY, Hiipakka RA, Kokontis JM, Warner KV, Xiang J, et al. The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells. Biochem Biophys Res Commun.2007;357:341-6.
[34]Hylemon PB, Gurley EC, Stravitz RT, Litz JS, Pandak WM, Chiang JY, et al. Hormonal regulation of cholesterol 7 alpha-hydroxylase mRNA levels and transcriptional activity in primary rat hepatocyte cultures. J Biol Chem.1992;267:16866-71.
[35]Ren S, Hylemon P, Marques D, Hall E, Redford K, Gil G, et al. Effect of increasing the expression of cholesterol transporters (StAR, MLN64, and SCP-2) on bile acid synthesis. J Lipid Res.2004;45:2123-31.
[36]Olle EW, Ren X, McClintock SD, Warner RL, Deogracias MP, Johnson KJ, et al. Matrix metalloproteinase-9 is an important factor in hepatic regeneration after partial hepatectomy in mice. Hepatology.2006;44:540-9.
[37]Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature.1996;383:728-31.
[38]Vidyashankar S, Varma SR, Azeemudin M, Godavarthi A, Krishna NS, Patki PS. A Novel Herbal Formulation "LiverCare" Differentially Regulates Primary Rat Hepatocyte and Hepatocarcinoma Cell Proliferation In Vitro. J Med Food.2011; 14:1023-31.
[39]Shimizu C, Fuda H, Yanai H, Strott CA. Conservation of the hydroxysteroid sulfotransferase SULT2B1 gene structure in the mouse:pre- and postnatal expression, kinetic analysis of isoforms, and comparison with prototypical SULT2A1. Endocrinology. 2003;144:1186-93.
[40]Hanley K, Wood L, Ng DC, He SS, Lau P, Moser A, et al. Cholesterol sulfate stimulates involucrin transcription in keratinocytes by increasing Fra-1, Fra-2, and Jun D. J Lipid Res. 2001;42:390-8.
[41]Zhang B, Cheng Q, Ou Z, Lee JH, Xu M, Kochhar U, et al. Pregnane X receptor as a therapeutic target to inhibit androgen activity. Endocrinology.2010; 151:5721-9.
[42]Chen Y, Chen X, Zhang S, Chen G. Influenza A virus infection activates cholesterol sulfotransferase (SULT2B1b) in the lung of female C57BL/6 mice. Biol Chem. 2011;392:869-76.
[43]Lees E, Faha B, Dulic V, Reed SI, Harlow E. Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with p107 and E2F in a temporally distinct manner. Genes Dev.1992;6:1874-85.
[44]Wang X, Krupczak-Hollis K, Tan Y, Dennewitz MB, Adami GR, Costa RH. Increased hepatic Forkhead Box M1B (FoxM1B) levels in old-aged mice stimulated liver regeneration through diminished p27Kip1 protein levels and increased Cdc25B expression. J Biol Chem. 2002;277:44310-6.
[45]Hanse EA, Nelsen CJ, Goggin MM, Anttila CK, Mullany LK, Berthet C, et al. Cdk2 plays a critical role in hepatocyte cell cycle progression and survival in the setting of cyclin Dl expression in vivo. Cell Cycle.2009;8:2802-9.
[46]Kim KH, Lee GY, Kim JI, Ham M, Won Lee J, Kim JB. Inhibitory effect of LXR activation on cell proliferation and cell cycle progression through lipogenic activity. J Lipid Res. 2010;51:3425-33.
[47]Choe SS, Choi AH, Lee JW, Kim KH, Chung JJ, Park J, et al. Chronic activation of liver X receptor induces beta-cell apoptosis through hyperactivation of lipogenesis:liver X receptor-mediated lipotoxicity in pancreatic beta-cells. Diabetes.2007;56:1534-43.
[48]Javitt NB, Lee YC, Shimizu C, Fuda H, Strott CA. Cholesterol and hydroxycholesterol sulfotransferases:identification, distinction from dehydroepiandrosterone sulfotransferase, and differential tissue expression. Endocrinology.2001; 142:2978-84.
[49]O'Callaghan YC, Woods JA, O'Brien NM. Oxysterol-induced cell death in U937 and HepG2 cells at reduced and normal serum concentrations. Eur J Nutr.1999;38:255-62.
[50]Bochelen D, Mersel M, Behr P, Lutz P, Kupferberg A. Effect of oxysterol treatment on cholesterol biosynthesis and reactive astrocyte proliferation in injured rat brain cortex. J Neurochem.1995:65:2194-200.
1. Michalopoulos, G. K., and M. C. DeFrances.1997. Liver regeneration. Science 276:60-66.
2. Fausto, N., J. S. Campbell, and K. J. Riehle.2006. Liver regeneration. Hepatology 43:S45-53.
3. Karp, S. J.2009. Clinical implications of advances in the basic science of liver repair and regeneration. Am J Transplant 9:1973-1980.
4. Michalopoulos, G. K.2010. Liver regeneration after partial hepatectomy:critical analysis of mechanistic dilemmas. Am JPathol 176:2-13.
5. Makino, H., H. Shimizu, H. Ito, F. Kimura, S. Ambiru, A. Togawa, M. Ohtsuka, H. Yoshidome, A. Kato, H. Yoshitomi, S. Sawada, and M. Miyazaki.2006. Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy. World J Gastroenterol 12:2053-2059.
6. Bensinger, S. J., M. N. Bradley, S. B. Joseph, N. Zelcer, E. M. Janssen, M. A. Hausner, R. Shih, J. S. Parks, P. A. Edwards, B. D. Jamieson, and P. Tontonoz.2008. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell 134:97-111.
7. Blaschke, F., O. Leppanen, Y. Takata, E. Caglayan, J. Liu, M. C. Fishbein, K. Kappert, K. I. Nakayama, A. R. Collins, E. Fleck, W. A. Hsueh, R. E. Law, and D. Bruemmer.2004. Liver X receptor agonists suppress vascular smooth muscle cell proliferation and inhibit neointima formation in balloon-injured rat carotid arteries. Circ Res 95:e110-123.
8. Vedin, L. L., S. A. Lewandowski, P. Parini, J. A. Gustafsson, and K. R. Steffensen.2009. The oxysterol receptor LXR inhibits proliferation of human breast cancer cells. Carcinogenesis 30:575-579.
9. Lo Sasso, G., N. Celli, M. Caboni, S. Murzilli, L. Salvatore, A. Morgano, M. Vacca, T. Pagliani, P. Parini, and A. Moschetta.2010. Down-regulation of the LXR transcriptome provides the requisite cholesterol levels to proliferating hepatocytes. Hepatology 51:1334-1344.
10. Fukuchi, J., R. A. Hiipakka, J. M. Kokontis, S. Hsu, A. L. Ko, M. L. Fitzgerald, and S. Liao. 2004. Androgenic suppression of ATP-binding cassette transporter Al expression in LNCaP human prostate cancer cells. Cancer Res 64:7682-7685.
11. Chuu, C. P., R. A. Hiipakka, J. Fukuchi, J. M. Kokontis, and S. Liao.2005. Androgen causes growth suppression and reversion of androgen-independent prostate cancer xenografts to an androgen-stimulated phenotype in athymic mice. Cancer Res 65:2082-2084.
12. Nomiyama, T., and D. Bruemmer,2008. Liver X receptors as therapeutic targets in metabolism and atherosclerosis. Curr Atheroscler Rep 10:88-95.
13. Cook, I. T., Z. Duniec-Dmuchowski, T. A. Kocarek, M. Runge-Morris, and C. N. Falany. 2009.24-hydroxycholesterol sulfation by human cytosolic sulfotransferases:formation of monosulfates and disulfates, molecular modeling, sulfatase sensitivity, and inhibition of liver x receptor activation. Drug Me tab Dispos 37:2069-2078.
14. Bai, Q., L. Xu, G. Kakiyama, M. A. Runge-Morris, P. B. Hylemon, L. Yin, W. M. Pandak, and S. Ren.2011. Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-lc signaling pathway in human aortic endothelial cells. Atherosclerosis 214:350-356.
15. Bjorkhem, I.2002. Do oxysterols control cholesterol homeostasis? J Clin Invest 110:725-730.
16. Chen, W., G. Chen, D. L. Head, D. J. Mangelsdorf, and D. W. Russell 2007. Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab 5:73-79.
17. Zhang, Z., D. Li, D. E. Blanchard, S. R. Lear, S. K. Erickson, and T. A. Spencer.2001. Key regulatory oxysterols in liver:analysis as delta4-3-ketone derivatives by HPLC and response to physiological perturbations. J Lipid Res 42:649-658.
18. Taub, R.2004. Liver regeneration:from myth to mechanism. Nat Rev Mol Cell Biol 5:836-847.
19. Locker, J., J. Tian, R. Carver, D. Concas, C. Cossu, G. M. Ledda-Columbano, and A. Columbano.2003. A common set of immediate-early response genes in liver regeneration and hyperplasia. Hepatology 38:314-325.
20. Xu, L., Q. Bai, D. Rodriguez-Agudo, P. B. Hylemon, D. M. Heuman, W. M. Pandak, and S. Ren.2010. Regulation of hepatocyte lipid metabolism and inflammatory response by 25-hydroxycholesterol and 25-hydroxycholesterol-3-sulfate. Lipids 45:821-832.
21. Xu, L., S. Shen, Y. Ma, J. K. Kim, D. Rodriguez-Agudo, D. M. Heuman, P. B. Hylemon, W. M. Pandak, and S. Ren.2012.25-Hydroxycholesterol-3-Sulfate (25HC3S) Attenuates Inflammatory Response via PPARgamma Signaling in Human THP-1 Macrophages. Am J Physiol Endocrinol Metab.
22. Schroepfer, G. J., Jr.2000. Oxysterols:modulators of cholesterol metabolism and other processes. Physiol Rev 80:361-554.
23. Ma, Y., L. Xu, D. Rodriguez-Agudo, X. Li, D. M. Heuman, P. B. Hylemon, W. M. Pandak, and S. Ren.2008.25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-I signaling pathway. Am J Physiol Endocrinol Metab 295:E1369-1379.
1. Vlahcevic, Z. R., W. M. Pandak, and R. T. Stravitz.1999. Regulation of bile acid biosynthesis. Gastroenterol Clin North Am 28:1-25, v.
2. Pandak, W. M., D. M. Heuman, P. B. Hylemon, and Z. R. Vlahcevic.1990. Regulation of bile acid synthesis. IV. Interrelationship between cholesterol and bile acid biosynthesis pathways. J Lipid Res 31:79-90.
3. Chiang, J. Y.2003. Bile acid regulation of hepatic physiology. Ⅲ. Bile acids and nuclear receptors. Am J Physiol Gastrointest Liver Physiol 284:G349-356.
4. Hylemon, P. B., R. T. Stravitz, and Z. R. Vlahcevic.1994. Molecular genetics and regulation of bile acid biosynthesis. Prog Liver Dis 12:99-120.
5. Goodwin, B., M. A. Watson, H. Kim, J. Miao, J. K. Kemper, and S. A. Kliewer.2003. Differential regulation of rat and human CYP7A1 by the nuclear oxysterol receptor liver X receptor-alpha. Mol Endocrinol 17:386-394.
6. Fu, X., J. G. Menke, Y. Chen, G. Zhou, K. L. MacNaul, S. D. Wright, C. P. Sparrow, and E. G. Lund.2001,27-hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells. J Biol Chem 276:38378-38387.
7. Javitt, N. B.2002. Cholesterol, hydroxycholesterols, and bile acids. Biochem Biophys Res Commun 292:1147-1153.
8. Meir, K., D. Kitsberg, I. Alkalay, F. Szafer, H. Rosen, S. Shpitzen, L. B. Avi, B. Staels, C. Fievet, V. Meiner, I. Bjorkhem, and E. Leitersdorf.2002. Human sterol 27-hydroxylase (CYP27) overexpressor transgenic mouse model. Evidence against 27-hydroxycholesterol as a critical regulator of cholesterol homeostasis. J Biol Chem 111:34036-34041.
9. O'Callaghan, Y. C., J. A. Woods, and N. M. O'Brien.1999. Oxysterol-induced cell death in U937 and HepG2 cells at reduced and normal serum concentrations. Eur J Nutr 38:255-262.
10. Corsini, A., D. Verri, M. Raiteri, P. Quarato, R. Paoletti, and R. Fumagalli.1995. Effects of 26-aminocholesterol,27-hydroxycholesterol, and 25-hydroxycholesterol on proliferation and cholesterol homeostasis in arterial myocytes. Arterioscler Thromb Vasc Biol 15:420-428.
11. Meng, Z., N. Liu, X. Fu, X. Wang, Y. D. Wang, W. D. Chen, L. Zhang, B. M. Forman, and W. Huang.2011. Insufficient bile acid signaling impairs liver repair in CYP27(-/-) mice. J Hepatol 55:885-895.
12. Ren, S., P. Hylemon, Z. P. Zhang, D. Rodriguez-Agudo, D. Marques, X. Li, H. Zhou, G. Gil, and W. M. Pandak.2006. Identification of a novel sulfonated oxysterol,5-cholesten-3beta,25-diol 3-sulfonate, in hepatocyte nuclei and mitochondria. J Lipid Res 47:1081-1090.
13. Pandak, W. M., S. Ren, D. Marques, E. Hall, K. Redford, D. Mallonee, P. Bohdan, D. Heuman, G. Gil, and P. Hylemon.2002. Transport of cholesterol into mitochondria is rate-limiting for bile acid synthesis via the alternative pathway in primary rat hepatocytes. J Biol Chem 277:48158-48164.
14. Ren, S., P. Hylemon, D. Marques, E. Hall, K. Redford, G. Gil, and W. M. Pandak.2004. Effect of increasing the expression of cholesterol transporters (StAR, MLN64, and SCP-2) on bile acid synthesis. J Lipid Res 45:2123-2131.
15. Li, X., W. M. Pandak, S. K. Erickson, Y. Ma, L. Yin, P. Hylemon, and S. Ren.2007. Biosynthesis of the regulatory oxysterol,5-cholesten-3beta,25-diol 3-sulfate, in hepatocytes. J Lipid Res 48:2587-2596.
16. Ma, Y., L. Xu, D. Rodriguez-Agudo, X. Li, D. M. Heuman, P. B. Hylemon, W. M. Pandak, and S. Ren.2008.25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. Am J Physiol Endocrinol Metab 295:E1369-1379.
17. Lo Sasso, G., N. Celli, M. Caboni, S. Murzilli, L. Salvatore, A. Morgano, M. Vacca, T. Pagliani, P. Parini, and A. Moschetta.2010. Down-regulation of the LXR transcriptome provides the requisite cholesterol levels to proliferating hepatocytes. Hepatology 51:1334-1344.
18. Bensinger, S. J., M. N. Bradley, S. B. Joseph, N. Zelcer, E. M. Janssen, M. A. Hausner, R. Shih, J. S. Parks, P. A. Edwards, B. D. Jamieson, and P. Tontonoz.2008. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell 134:97-111.
19. Blaschke, F., O. Leppanen, Y. Takata, E. Caglayan, J. Liu, M. C. Fishbein, K. Kappert, K. I. Nakayama, A. R. Collins, E. Fleck, W. A. Hsueh, R. E. Law, and D. Bruemmer.2004. Liver X receptor agonists suppress vascular smooth muscle cell proliferation and inhibit neointima formation in balloon-injured rat carotid arteries. Circ Res 95:e110-123.
20. Vedin, L. L., S. A. Lewandowski, P. Parini, J. A. Gustafsson, and K. R. Steffensen.2009. The oxysterol receptor LXR inhibits proliferation of human breast cancer cells. Carcinogenesis 30:575-579.
21. Kim, K. H., G. Y. Lee, J. I. Kim, M. Ham, J. Won Lee, and J. B. Kim.2010. Inhibitory effect of LXR activation on cell proliferation and cell cycle progression through lipogenic activity. J Lipid Res 51:3425-3433.
22. Fukuchi, J., J. M. Kokontis, R. A. Hiipakka, C. P. Chuu, and S. Liao.2004. Antiproliferative effect of liver X receptor agonists on LNCaP human prostate cancer cells. Cancer Res 64:7686-7689.
23. Ren, S., X. Li, D. Rodriguez-Agudo, G. Gil, P. Hylemon, and W. M. Pandak.2007. Sulfated oxysterol,25HC3S, is a potent regulator of lipid metabolism in human hepatocytes. Biochem Biophys Res Commun 360:802-808.
24. Qianming Bai, X. Z., Leyuan Xu, Genta Kakiyama, Douglas Heuman, Arun Sanyal, William M. Pandak, Lianhua Yin, Wen Xie, Shunlin Ren. Oxysterol sulfation by cytosolic sulfotranseferase suppresses liver X receptor/sterol regulatory element binding protein-lc signaling pathway and reduces serum and hepatic lipids in mouse models of nonalcohol fatty liver disease. Metabolism.
25. Wang, X., K. Krupczak-Hollis, Y. Tan, M. B. Dennewitz, G. R. Adami, and R. H. Costa. 2002. Increased hepatic Forkhead Box M1B (FoxM1B) levels in old-aged mice stimulated liver regeneration through diminished p27Kipl protein levels and increased Cdc25B expression. J Biol Chem 111:44310-44316.
26. Huff, V.2011. Wilms'tumours:about tumour suppressor genes, an oncogene and a chameleon gene. Nat Rev Cancer 11:111-121.
27. Kelman, Z.1997. PCNA:structure, functions and interactions. Oncogene 14:629-640.
28. Harbour, J. W., and D. C. Dean.2000. The Rb/E2F pathway:expanding roles and emerging paradigms. Genes Dev 14:2393-2409.
29. Zachariae, W., and K. Nasmyth.1999. Whose end is destruction:cell division and the anaphase-promoting complex. Genes Dev 13:2039-2058.
30. Matsuoka, S., M. Huang, and S. J. Elledge.1998. Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 282:1893-1897.
31. Cain, K.2003. Chemical-induced apoptosis:formation of the Apaf-1 apoptosome. Drug Metab Rev 35:337-363.
32. Li, X., P. Hylemon, W. M. Pandak, and S. Ren.2006. Enzyme activity assay for cholesterol 27-hydroxylase in mitochondria. J Lipid Res 47:1507-1512.
33. Xu, L., Q. Bai, D. Rodriguez-Agudo, P. B. Hylemon, D. M. Heuman, W. M. Pandak, and S. Ren.2010. Regulation of hepatocyte lipid metabolism and inflammatory response by 25-hydroxycholesterol and 25-hydroxycholesterol-3-sulfate. Lipids 45:821-832.
34. Bai, Q., L. Xu, G. Kakiyama, M. A. Runge-Morris, P. B. Hylemon, L. Yin, W. M. Pandak, and S. Ren.2011. Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-lc signaling pathway in human aortic endothelial cells. Atherosclerosis 214; 350-356.
35. Nilsson,1., and I. Hoffmann.2000. Cell cycle regulation by the Cdc25 phosphatase family. Prog Cell Cycle Res 4:107-114.
36. Sebastian, B., A. Kakizuka, and T. Hunter.1993. Cdc25M2 activation of cyclin-dependent kinases by dephosphorylation of threonine-14 and tyrosine-15. Proc Natl A cad Sci USA 90: 3521-3524.
37. Trembley, J. H., J. O. Ebbert, B. T. Kren, and C. J. Steer.1996. Differential regulation of cyclin B1 RNA and protein expression during hepatocyte growth in vivo. Cell Growth Differ 7:903-916.
38. Sohn, V. R., A. Giros, R. M. Xicola, L. Fluvia, M. Grzybowski, A. Anguera, and X. Llor. 2011. Stool-fermented Plantago ovata husk induces apoptosis in colorectal cancer cells independently of molecular phenotype. Br J Nutr:1-12.
39. Petry, I. B., E. Fieber, M. Schmidt, M. Gehrmann, S. Gebhard, M. Hermes, W. Schormann, S. Selinski, E. Freis, H. Schwender, M. Brulport, K. Ickstadt, J. Rahnenfuhrer, L. Maccoux, J. West, H. Kolbl, M. Schuler, and J. G. Hengstler.2010. ERBB2 induces an antiapoptotic expression pattern of Bcl-2 family members in node-negative breast cancer. Clin Cancer Res 16:451-460.
40. Vedin, I., T. Cederholm, Y. Freund-Levi, H. Basun, E. Hjorth, G. F. Irving, M. Eriksdotter-Jonhagen, M. Schultzberg, L. O. Wahlund, and J. Palmblad.2010. Reduced prostaglandin F2 alpha release from blood mononuclear leukocytes after oral supplementation of omega3 fatty acids:the OmegAD study. J Lipid Res 51:1179-1185.
41. Coughtrie, M. W., S. Sharp, K. Maxwell, and N. P. Innes.1998. Biology and function of the reversible sulfation pathway catalysed by human sulfotransferases and sulfatases. Chem Biol Interact 109:3-27.
42. Falany, C. N.1997. Enzymology of human cytosolic sulfotransferases. FASEB J 11:206-216.
43. Strott, C. A.2002. Sulfonation and molecular action. Endocr Rev 23:703-732.
44. Falany, C. N., D. He, N. Dumas, A. R. Frost, and J. L. Falany.2006. Human cytosolic sulfotransferase 2B1:isoform expression, tissue specificity and subcellular localization. J Steroid Biochem Mol Biol 102:214-221.
45. He, D., A. R. Frost, and C. N. Falany.2005. Identification and immunohistochemical localization of Sulfotransferase 2B1b (SULT2B1b) in human lung. Biochim Biophys Acta 1724:119-126.
46. He, D., C. A. Meloche, N. A. Dumas, A. R. Frost, and C. N. Falany.2004. Different subcellular localization of sulphotransferase 2B1b in human placenta and prostate. Biochem J 379:533-540.
47. Higashi, Y., H. Fuda, H. Yanai, Y. Lee, T. Fukushige, T. Kanzaki, and C. A. Strott.2004. Expression of cholesterol sulfotransferase (SULT2B1b) in human skin and primary cultures of human epidermal keratinocytes. J Invest Dermatol 122:1207-1213.
48. Meinl, W., B. Ebert, H. Glatt, and A. Lampen.2008. Sulfotransferase forms expressed in human intestinal Caco-2 and TC7 cells at varying stages of differentiation and role in benzo[a]pyrene metabolism. Drug Me tab Dispos 36:276-283.
49. Yanai, H., N. B. Javitt, Y. Higashi, H. Fuda, and C. A. Strott.2004. Expression of cholesterol sulfotransferase (SULT2B1b) in human platelets. Circulation 109:92-96.
50. Fuda, H., Y. C. Lee, C. Shimizu, N. B. Javitt, and C. A. Strott.2002. Mutational analysis of human hydroxysteroid sulfotransferase SULT2B1 isoforms reveals that exon 1B of the SULT2B1 gene produces cholesterol sulfotransferase, whereas exon 1A yields pregnenolone sulfotransferase. J Biol Chem 277:36161-36166.
51. Meloche, C. A., and C. N. Falany.2001. Expression and characterization of the human 3 beta-hydroxysteroid sulfotransferases (SULT2B1a and SULT2B1b). J Steroid Biochem Mol Biol 77:261-269.
52. Fuda, H., N. B. Javitt, K. Mitamura, S. Ikegawa, and C. A. Strott.2007. Oxysterols are substrates for cholesterol sulfotransferase. JLipid Res 48:1343-1352.
53. Cook, I. T., Z. Duniec-Dmuchowski, T. A. Kocarek, M. Runge-Morris, and C. N. Falany. 2009.24-hydroxycholesterol sulfation by human cytosolic sulfotransferases:formation of monosulfates and disulfates, molecular modeling, sulfatase sensitivity, and inhibition of liver x receptor activation. Drug Metab Dispos 37:2069-2078.
54. Chen, W., G. Chen, D. L. Head, D. J. Mangelsdorf, and D. W. Russell.2007. Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab 5:73-79.
55. Schroepfer, G. J., Jr.2000. Oxysterols:modulators of cholesterol metabolism and other processes. Physiol Rev 80:361-554.
56. Snyder, V. L., M. Turner, P. K. Li, A. El-Sharkawy, G. Dunphy, and D. L. Ely.2000. Tissue steroid sulfatase levels, testosterone and blood pressure. J Steroid Biochem Mol Biol 73:251-256.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |