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油菜素内酯调控番茄农药降解的生理与分子机制
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摘要
农药的使用已成为防治植物病虫害、去除杂草、调节农作物生长、实现农业机械化及提高农产品产量和质量的重要措施。然而,在集约化的设施生产条件下,病虫害高发频发,导致化学农药的大量使用,常常引起蔬菜等农作物产生药害以及高超标的农药残留。这不仅直接危害人类健康和生存环境,而且国际贸易中也不断发生因农药问题引起的贸易摩擦。因此,研究农药对蔬菜作物生长的影响以及如何降低蔬菜中的农药残留,对实现蔬菜高效、安全生产和发展可持续农业具有重要意义。本文以番茄(Lycopersicon esculentum Mill.)为材料,以生产中普遍使用的百菌清、多菌灵、毒死蜱和联苯菊酯为目标化合物,研究了番茄对不同化学性质农药的响应机理。并结合番茄BRs野生型和合成缺失突变体材料,研究了BRs对农药药害的缓解以及促进农药降解的作用机理,同时探讨了H202在BRs促进农药降解中的信号作用。此外,我们利用基因芯片技术构建了植物对农药和BRs响应的表达谱,进一步阐明了BRs促进植物体内源农药降解代谢的分子机制。主要结果如下:
     1.研究了百菌清(CHT)、多菌灵(CAR)、毒死蜱(CPF)、联苯菊酯(BIF)4种农药对番茄生长,生理状态和解毒相关参数的影响。结果表明,2倍推荐剂量的4种农药对番茄的净光合速率(Pn)和叶绿素荧光参数均产生了不同程度的抑制作用。在处理杀菌剂CHT和杀虫剂CPF 24 h后显著地诱导了番茄中GSH合成,GST、GR、POD酶活力和解毒相关基因(GSH、GST1、GST2、GST3、GR和GPX)的上调。然而,杀菌剂CAR和杀虫剂BIF处理后却没有改变GSH含量、解毒酶活力和基因的表达水平。此外,CHT和CPF对GSH合成,解毒酶活力和解毒相关基因的诱导具有浓度和时间效应。
     2.研究了BRs缓解农药药害作用及对解毒酶和基因表达的影响。结果表明,野生型或突变体番茄预处理EBR后,能够明显的缓解CHT和CPF对Pn、ΦPSII,qP和Fv'/Fm'的抑制,并恢复到接近对照水平,并且野生型对CHT和CPF的抗性明显高于突变体。EBR显著促进了GSH的合成,并显著提高了还原型GSH的含量。同时,EBR诱导了GST和GR的活力上升,增强了解毒相关基因(CYP724B2, GSH1, GSH2, GST1, GST2, GST3, GR和ABC)的表达。
     3.BRs能够提高植物体内解毒酶活力、解毒基因表达和GSH含量,避免药害产生,然而这种机制也与BRs加速了植物体内农药降解代谢有关。不同浓度的外源EBR预处理显著的提高了CHT残留的降解速率,而且较低浓度的EBR预处理效果更显著。同时,野生型番茄上的CHT残留量显著的低于BRs合成缺失突变体,预处理EBR均能加速野生型和突变体CHT残留的降解,缩短农药残留在植物体内降解的半衰期。此外,研究还发现,抑制了GSH的合成,CHT的降解速率也显著减缓。表明BRs可能通过促进GSH的合成、解毒酶活力和解毒基因的表达而加速农药的降解。
     4.研究了H2O2在BRs促进农药降解代谢中的信号作用。外源处理不同浓度的EBR能够显著诱导内源H2O2的产生,并具有明显的浓度效应。野生型中H202含量高于突变体。预处理EBR能够同时诱导野生型和突变体H202含量的增加;而且H2O2的含量与RBOH表达密切相关。同时,我们利用NADPH氧化酶抑制剂(DPI),H2O2清除剂(DMTU)和NADPH合成抑制剂(6-AN)抑制内源H2O2爆发,发现抑制H2O2产生后,导致了GSH含量和解毒酶活力的降低,并显著抑制了解毒基因表达,同时也减缓了CHT在番茄体内的降解。然而外源预处理EBR或H2O2后,显著的提高了内源H2O2的含量,并诱导了GSH的合成,解毒酶活力的提高和解毒基因的表达,促进了CHT在番茄体内的降解。
     5.为了进一步明确农药药害产生和BRs促进农药降解的分子机理,我们利用Affymetrix GeneChip(?) Tomato Genome Array技术,分析了农药CHT,EBR和预处理EBR后再处理CHT对番茄转录组的影响。农药处理后共得到1545个有效的差异基因,其中上调670个,下调875个;单独EBR处理获得1584个有效差异基因,其中上调544个,下调1040个;预处理EBR后再处理CHT,得到1725个有效差异基因,其中上调700个,下调1025个。大量的基因受BRs和农药共同调控。经分子注释系统(Molecule Annotation System)分析发现,这些基因中大部分涉及了催化活性功能。EBR预处理诱导了共表达基因中许多涉及解毒功能的基因的高表达。同时发现,共调控基因中还涉及许多乙烯受体和乙烯响应的基因,说明BRs促进农药代谢过程可能与乙烯存在着互作。
Pesticides are important strategies for pest management, improvement of crop yield and quality, plant growth regulation as well as realization of agricultural mechanization. Presently, due to extensive use of chemical pesticides, especially in protected agriculture which involved frequent pesticides application, crops often suffers the pesticide injury and high pesticide residues, which not only directly harm human health and our living environment, but also cause international trade issues. For the development of sustainable agriculture, it is of great importance to study the mechanisms of plant adaptation to environmental stresses and explore the effective strategy to enhance the tolerance of vegetable crops and improve the productivity, quality and safety of agricultural produces. In this study, we have investigated the differences of plant in response to chlorothalonil (CHT), carbendazim (CAR), chlorpyrifos (CPF) and bifenthrin (BIF) by using tomato(Lycopersicon esculentum Mill.) as model plant. After that, the role and mechanism of brassinosteroids (BRs) alleviating pesticides phytotoxicity and promoting pesticide metabolism were investigated in wild type tomato with normal BRs level or mutant lack of BRs. Meanwhile, we have investigated the role of H2O2 in BRs promoting pesticides metabolism. In addition, Affymetrix GeneChip(?) Tomato Genome Array was utilized to further clarify the mechanism of BRs promoting pesticides metabolism. The results are as follows:
     1. We have investigated the effects of chlorothalonil (CHT), carbendazim (CAR), chlorpyrifos (CPF) and bifenthrin (BIF) on tomato plant growth and physiology as well as detoxification-related parameters. All pesticides used with double recommended dose inhibited photosynthesis and chlorophyll fluorescence parameters of tomato plant by different degrees. Both CHT and CPF treatments increased the content of reduced glutathione (GSH), activities of glutathione S-transferase (GST), glutathione reductase (GR) and peroxidase (POD), as well as transcriptional levels of detoxification-related genes (GSH, GST1, GST2, GST3, GR and GPX). However, in contrast, GSH content, enzyme activity and gene expression were not influenced significantly by CAR and BIF as compared to that of control. In addition, GST, GR, POD activities and most gene expression were induced by CHT and CPF in a concentration-and time-dependent manner.
     2. The effects of BRs on alleviation of pesticides injury, detoxification-related enzyme activities and gene expression were investigated in tomato wild type (WT) and mutant (M). The inhibition effects of CHT and CPF on parameters of photosynthesis and chlorophyll fluorescence were alleviated by pretreatment with EBR. Moreover, WT plants exhibited higher tolerance to pesticides than M plants. BRs increased GSH content, GST and GR activities and transcriptional levels of CYP724B2, GSH1, GSH2, GST1, GST2, GST3, GR and ABC.
     3. We have investigated the effects of BRs on pesticide residue and the mechanism of its promoting pesticide degradation. All the concentrations of EBR set in this experiment increased CHT degradation rate. It is more effective to use lower EBR concentration. The pesticide residue of WT was lower than that of M. Furthermore, BRs had shortened half-life of pesticide residue. In addition, the degradation rate of pesticide residue was slowed down by inhibition of GSH synthesis.
     4. The signal role of H2O2 in that of BRs promoting pesticide degradation was investigated. The different concentrations of EBR significantly increased the endogenous H2O2 content, which exhibited a concentration-dependent manner. WT plants had a higher H2O2 content than that of M plants. The content of H2O2 in WT or M plants was also increased by pretreatment with EBR. The H2O2 content was closely related to the expression of gene RBOH. The content of H2O2 was inhibited by using NADPH oxidase inhibitor (DPI), H2O2 eliminator (DMTU) and NADPH inhibitor (6-AN). After inhibiting H2O2 burst, we observed that the CHT residue degradation rate was slowed down markedly with the decline in GSH content, detoxification-related enzyme activities and gene expression. In contrast, pretreatment with exogenous EBR and H2O2 significantly increased GSH content, detoxification-related enzyme activities and gene expression, resulting in lower pesticide residue as compared with that of control.
     5. Affymetrix GeneChip(?) Tomato Genome Array was utilized to further clarify the mechanism of BRs promoting pesticides metabolism. There are total of 1545 different expression genes by CHT treatment,670 of up-regulated genes and 875 down-regulated genes. EBR treatment induced 1584 different expression genes,544 of up-regulated genes and 1040 down-regulated genes. EBR&CHT treatment induced 1725 different expression genes,700 of up-regulated genes and 1025 down-regulated genes. Among these different expression genes, most genes were co-regulated by both BRs and CHT. Analyzing by molecule annotation system, we found that these genes involved many molecular functions and the percentage of gene function was dominated by catalytic category. Moreover, many co-regulated genes were involved in the function of detoxification-related process such as P450, transferases and transporters. Meanwhile, there were also some ethylene (ET) receptor and response genes among the co-regulated genes, which suggested that there may be crosstalk between BRs and ET in process of BRs promoting pesticide degradation.
引文
林玉锁,龚瑞忠,朱忠林.(2000)农药与生态环境保护,北京:化学工业出版社,7-8.
    王谢民.(2009)中国农药出口现状与发展前景浅析。科学论坛24:197.
    虞云龙,盛国英,傅家漠.(1999)农药降解酶的固定化及其降解特性.应用与环境生物学报,增刊:166-169.
    Aach J, Rindone W, Church GM. (2000) Systematic management and analysis of yeast gene expression data. Genome Res.10:431-445.
    Aharon IA, Vorst 0. (2002) DNA microarrays for functional plant genomics. Plant Mol.Biol.48:99-118.
    Aislabie J, Lloyd-Jones G. (1995) A review of bacteria-degradation of pesticides. Austral. J. Soil Res.33:925-942.
    Aksu Z. (2005) Application of biosortion for removal of organic pollutants:a review. Process Biochem 40:997-1026.
    Anuradha S, Rao SSR. (2001) Effect of brassinosteroids on salinity stress induced inhibition of seed germination and seedling growth of rice (Oryza sativa L.). Plant Growth Regul.33:151-153.
    Armstrong RN. (1994) Glutathione S-transferases:structure and mechanism of an archetypical detoxification enzyme. Adv. Enzymol. Relat. Areas Mol. Biol.69: 1-44.
    Asada K. (2000) The water-water cycle as alternative photon and electron sinks. Philos. Trans. R. Soc. London B 355:1419-1431.
    Audus LJ. (1951) The biological-detoxification of hormone herbicides in soil. Plant soil.3:170-192.
    Bai MY; Zhang LY, Gampala SS, Zhu SW, Song WY, Chong K, Wang ZY. (2007) Functions of OsBZR1 and 14-3-3 proteins in brassinosteroid signaling in rice. Proc. Natl. Acad. Sci. USA 104:13839-13844.
    Bajguz A, Hayat S. (2009) Effects of brassinosteroids on the plant responses to
    environmental stresses. Plant Physiol. Biochem.47:1-8.
    Ball L, Accotto GP, Bechtold U, Creissen G, Funck D. (2004) Evidence for a direct link between glutathione biosynthesis and stress defense gene expression in Arabidopsis. Plant Cell 16:2448-2462.
    Barbagallo RP, Oxborough K, Pallett KE, Baker NR. (2003) Rapid, noninvasive screening for perturbations of metabolism and plant growth using chlorophyll fluorescence imaging. Plant Physiol.132:485-493.
    Barrett M. (2000) The role of cytochrome P450 enzymes in herbicide metabolism. Pages 25-37 in A. H. Cobbs and R. C. Kirkwood, eds. Herbicides and Their Mechanisms of Action. Sheffield, Great Britain:Sheffield Academic.
    Baxter-Burrell A, Yang Z, Springer PS, Bailey-Serres J. (2002) RopGAP4-dependent Rop GTPase rheostat control of Arabidopsis oxygen deprivation tolerance. Science 296:2026-2028.
    Bhatti MA, Al-Khatib K, Felsot AS, Parker R, Kadir S. (1995) Effects of simulated chlorsulfuron drift on fruit yield and quality of sweet cherries (Prunus avium L.). Environ Toxicol Chem 14:537-544.
    Bishop GJ, Koncz C. (2002) Brassinosteroids and plant steroid hormone signaling. Plant Cell 14:S97-S110.
    Boettner GH, Elkinton JS, Boettner CJ. (2000) Effects of a biological control introduction on three nontarget native species of saturniid moths. Cons Biol 14: 1798-1806.
    Bolwell G, Bozak PK, Zimmerlin A. (1994) Plant cytochrome P450. Phytochemistry 37:1491-1505.
    Boutin C, Lee HB, Peart ET, Batchelor PS, Maguire RJ. (2000) Effects of the sulfonylurea herbicide metsulfuron-methyl on growth and reproduction of five wetland and terrestrial plant species. Environ Toxicol Chem 1.9:2532-2541.
    Brazier-Hicks M, Evans KM, Cunningham OD, Hodgson DRW, Steel PG, Edwards R. (2008) Catabolism of glutathione conjugates in Arabidopsis thaliana-Role in metabolic reactivation of the herbicide safener fenclorim. J. Biol. Chem.283: 21102-21112.
    Brenner V, Arensdorf JJ, Focht DD. (1994) Genetic construction of PCB degraders. Biodegradation 5:359-377.
    Cabanne F, Huby D, Gaillardon P, Scalla R, Durst F. (1987) Effect of the cytochrome P-450 inactivator 1-aminobenzotriazole on the metabolism of chlortoluron and isoproturon in wheat. Pest. Biochem. Physiol.28:371-380.
    Cakmak I, Marschner H. (1992) Magnesium deficiency and high light intensity enhance activities, superoxide dismutase ascorbate peroxidase, and glutathione reductase in bean leaves. Plant Physiol.98:1222-1227.
    Canivenc M, Cagnac CB, Cabanne F, Scalla R. (1989) Induced changes of chlorotoluron metabolism in wheat cell suspension cultures. Plant Physiol. Biochem.27:193-201.
    Cardinale BJ, Harvey CT, Gross K, Ives AR. (2003) Biodiversity and biocontrol: emergent impacts of a multi-enemy assemblage on pest suppression and crop yield in an agroecosystem. Ecol Let 6:857-865.
    Carol RJ, Dolan L. (2006) The role of reactive oxygen species in cell growth:lessons from root hairs. J.Exp. Bot.57:1829-1834.
    Casida JE, Fujioka K. (2007) Glutathione S-Transferase Conjugation of Organophosphorus Pesticides Yields S-Phospho-, S-Aryl-, and S-Alkylglutathione Derivatives Chem. Res. Toxicol.20:1211-1217.
    Caux PY, Kent RA, Fan GT, Stephenson GL. (1996) Environmental fate and effects of chlorothalonil:A Canadian perspective. Crit. Rev. Environ. Toxicol. Chem.26: 45-93.
    Cedergreen N, Streibig JC. (2005) The toxicity of herbicides to non-target aquatic plants and algae:assessment of predictive factors and hazard. Pest Manag. Sci. 61:1152-1160.
    Chinchilla D, Zipfel C, Robatzek S, Kemmerling B, Nurnberger T, Jones JD, Felix G, Boller T. (2007) A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence. Nature 448:497-500.
    Clouse SD. (1998) Brassinolide affects the rate of cell division in isolated leaf protoplastof Petunia hybrida. Plant cell Rep.49:427-451.
    Clouse SD, Daniel ME. (1992) Effect of brassinolide on gene expression in elongating soybean epicotyls. Plant physiol.100:1377-1383.
    Clouse SD, Sasse JM. (1998) Brassinosteroids:essential regulators of plant growth and development. Annu. Rev. Plant Physiol. Plant Mol. Biol.49:427-451.
    Clouse SD, Zurek DM. (1991) Molecular analysis of brassinolide action in plant growth and development. In:Brassinosteroids chemistry, bioactivity and application. Washington DC, America Chemical Society. pp:122-140.
    Cole D, Cummins I, Hatton P, Dixon D, Edwards R. (1997) Glutathione transferases in crops and major weeds. In KK Hatzios, ed, Regulation of Enzymatic Systems Detoxifying Xenobiotics in Plants. Kluwer Academic Publishers, Amsterdam. pp: 139-154.
    Cole DJ Edwards R. (2000) Secondary metabolism of agrochemicals in plants. In Agrochemicals and Plant Protection (Roberts, T.R., ed.). London:John Wiley and Sons pp.107-154.
    Coleman JOD, Blake-Kalff MMA, Davies TGE. (1997) Detoxification of xenobiotics by plants:chemical modification and vacuolar compartmentation. Trends Plant Sci.2:144-151.
    Cutker GC. (1991) Brassinosteriods through the looking glass:an appraisal. In:Cutler HG, Yokata T, Adam G (eds.) Brassinosteroids Chemistry, Bioactivity, and Applications. Washington DC, American Chemical Society.pp:334-345.
    Dalle-Donne I, Rosii R, Colombo G, Giustarini D, Milzani A. (2009) Protein S-glutathionylation:a regulatory device from bacteria to humans. Trends Biochem. Sci.34:85-96.
    Dat JF, Lopez-Delgado H, Foyer CH, Scott IM. (1998) Parallel changes in H2O2 and catalase during thermotolerance induced by salicylic acid or heat acclimation in mustard seedlings. Plant Physiol.116:1351-1357.
    Davies PE, White RWG. (1985) The toxicology and metabolism of chlorothalonil in fish. I. Lethal levels for Salmo gairdneri, Galaxis maculatus, G. truttaceus, G. auratus and the fate of 14C TCIN gairdneri. Aquat. Toxicol.7:93-105.
    Deneke SM, Fanburg BL (1989) Regulation of cellular glutathione. Am. Physiol Soc.
    257:L163-L173
    Deng F, Hatzios KK. (2002) Purification and characterization of two glutathione S-transferase isozymes from Indica-Type rice involved in herbicide detoxification. Pest. Biochem. Physiol.72:10-23.
    Deng L, Qu H, Huang R, Yang Y, Zheng X,Wang, H. (2003) Survey of food poisoning by organophosphorus pesticide at an employee refectory. Practical Preventive Medicine 10:766-767.
    Desikan R, A-H-Mackerness S, Hancock JT, Neill SJ. (2001) Regulation of the Arabidopsis transcriptome by oxidative stress. Plant Physiol.127:159-172.
    Dhaubhadel S, Browning KS, Gallie DR, Krishna P. (2002) Brassinosteroid functions to protect the translational machinery and heat-shock protein synthesis following thermal stress. Plant J.29:681-691.
    Dua M, Singh A, Sethunathan N, Johri A. (2002) Biotechnology and bioremediation: successes and limitations. Appl. Microbiol. Biotechnol.59:142-152.
    Duran N, Esposito E. (2000) Potential applications of oxidative enzymes and phenoloxidase-like compounds in wastewater and soil treatment:a review. Appl. Catal. B:Environ.28:83-99.
    Edgehil RU, Fin PK. (1983) Microbial treatment of soil to remove pentachlorophenol. Appl. Environ. Microbiol.45:1122-1125.
    Edwards R, Dixon DP, Walbot V. (2000) Plant glutathione S-transferases:enzymes with multiple functions in sickness and in health. Trends in Plant Science 5: 193-198.
    Erickson BD, Mondello FJ. (1992) Nucleotide sequencing transcriptional mapping of the genes encoding biphenyl dioxygenase, a multicomponent polychlorinated-biphenyl-degrading enzyme in Pseudomonas strain-LB400. J Bacteriol.174:2903-2912.
    Ershova A, Khripach V. (1996) Effect of epibrassinolide on lipid peroxidation in Pisum sativum at normal aeration and under oxygen deficiency. Russian Journal of Plant Physiol.43:750-752.
    Faria LDB, Umbanhowar J, McCann KS. (2008) The long term and transient implications of multiples predators in biocontrol. Theor. Ecol.1:45-53.
    Farkas MH, Berry JO, AGA DS. (2007) Chlortetracycline detoxification in maize via induction of glutathione S-transferases after antibiotic exposure. Environ. Sci. Technol.41:1450-1456.
    Farkas MH, Berry JO, AGA DS. (2007) Chlortetracycline detoxification in maize via induction of glutathione S-transferases after antibiotic exposure. Environ. Sci. Technol.41:1450-1456.
    Foght J, April T, Biggar K, Aisabie J. (2001) Bioremediation of DDT-contaminated soils:A review, Bioremediation J.5:225-246.
    Foyer CH, Halliwell B. (1976) The presence of glutathione and glutathione reductase in chloroplasts:a proposed role in ascorbic arid metabolism. Planta 133:21-25.
    Frazar C. (2000) The bioremediation and phytoremediation of pesticide-contaminated sites, National network of environmental studies (NNEMS) fellow, Washington DC.
    Frear DS, Swanson HR. (1970) Biosynthesis of S-(4-ethylamino-6-isopropylamino-2-s-triazine) glutathione:partial purification and properties of glutathione S-transferase from corn. Phytochemistry 9: 2123-2132.
    Fujisawa T, Kurosawa M, Katagi T. (2006) Uptake and transformation of pesticide metabolites by duckweed (Lemna gibba). J. Agri. Food Chem.54:6286-6293.
    Funk SB, Crawford DL, Crawford RL. (1995) Full-scale anaerobic bioremediation of trinitrotoluene (TNT) contaminated soil:a US EPA site Program demonstration. Applied Biochemistry and Biotechnology Part A:Enzyme Engineering and Biotechnology. (51-52):625-633.
    Furukawa K. (2000) Engineering dioxygenases for efficient degradation of environmental pollutants. Curr. Opin. Biotechnol.11:244-249.
    Gaillardon P, Cabanne F, Scalla R, Durst F. (1985) Effect of mixed function oxidase inhibitors on the toxicity of chlortoluron and isoproturon to wheat. Weed Res.25: 397-402.
    Gampala SS, Kim TW, He JX, et al. (2007) An essential role for 14-3-3 proteins in brassinosteroid signal transduction in Arabidopsis. Dev. Cell 13:177-189.
    Garcia O, Bouige P, Forestier C, Dassa E. (2004) Inventory and comparative analysis of rice and Arabidopsis ATP-binding cassette (ABC) systems. J. Mol. Biol.343:249-265.
    Gendron JM, Wang ZY. (2007) Multiple mechanisms modulate brassinosteroid signaling. Curr. Opin. Plant Biol.10:436-441.
    Genty B, Briantais JM, Baker NR. (1989) The relationship between the quantum yield of photosynthetic electron transport and quenching of chlorophyll fluorescence. Biochimica et Biophysica Acta 990:87-92.
    Goda H, Shimada Y, Asami T, Fujioka S, Yoshida S. (2002) Microarray analysis of Brassinosteroid-regulated genes in Arabidopsis. Plant Physiol. 130:1319-1334.
    Grove MD, Spencer GF, Rohwedder WK, Mandava N, Worley JF, JR Warthen JD, Steffens GL, Flippen-Anderson JL, JR Cook JC. (1979) Brassinolide:a plant growth-promoting steroid isolated from Brassinca napus pollen. Nature 281: 216-217.
    Grzywacz D, Rossbach A, Rauf A, Russell DA, Srinivasan R, Shelton AM. (2010) Current control methods for diamondback moth and other brassica insect pests and the prospects for improved management with lepidopteran-resistant Bt vegetable brassicas in Asia and Africa. Crop protection 29:68-79.
    Hall JC, Hoagland RE, Zoblotowicz RM. (2001) Pesticide Biotransformation in Plants and Microorganisms:Similarities and Divergences. ACS symposium series 777, Washington, D. C.432.
    Hatzios KK, Burgos N. (2004) Metabolism-based herbicide resistance:regulation by safeners. Weed Sci.52:454-467.
    Haubrick LL, Assmann SM. (2006) Brassinosteroids and plant function:some clues, more puzzles. Plant Cell Environ.29:446-457.
    Hayes TB, Collins A, Lee M, Mendoza M, Noriega N, Stuart AA, Vonk A. (2001) Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses. Proc. Natl. Acad. Sci. USA 99:5476-5480.
    He K, Gou X, Yuan T, Lin H, Asami T, Yoshida S, Russell SD, Li J. (2007) BAK1 and BKK1 regulate brassinosteroid-dependent growth and brassinosteroid-independent cell-death pathways. Curr. Biol.17:1109-1115.
    Heese A, Hann DR, Gimenez-Ibanez S, Jones AM, He K, Li J, Schroeder JI, Peck SC, Rathjen JP. (2007) The receptor-like kinase SERK3/BAK1 is a central regulator of innate immunity in plants. Proc. Natl. Acad. Sci. USA.104:12217-12222.
    Hoagland RE, Zablotowicz RM. (2001) The role of plant and microbial hydrolytic enzymes in pesticide metabolism. In Pesticide Biotransformation in Plants and Microorganisms:Similarities and Divergences, [Hall JC, Hoagland RE, Zoblotowicz RM, Editors]. ACS symposium series 777, Washington, D. C. pp: 58-88.
    Hrywna Y, Tsoi TV, Maltseva OV, Quensen JF, Tiedje JM. (1999) Construction and characterization of two recombinant bacteria that grow on ortho-and para-substituted chlorobiphenyls. Appl. Environ. Microbiol.65:2163-2169.
    Hu H, You J, Fang Y, Zhu X, Qi Z, Xiong L. (2008) Characterization of transcription factor gene SNAC2 conferring cold and salt tolerance in rice. Plant Mol. Biol.67: 169-181.
    Ikekawa N, Zhao YJ. (1981) Application of 24-epibrassinolid in agriculture. In:Cutler HG, Yokota T, Adam G (eds) Brassinosteroids, Chemistry, Bioactivity and Applications. ACS Symposium Series. American Chemical Society, Washington DC. pp:280-291.
    Ishii M, Hashimoto S, Tsutsumi S, Wada Y, Matsushima K, Kodama T, Aburatani H. (2000) Direct comparison of GeneChip and SAGE on the quantitative accuracy in transcript profiling analysis. Genomics 68:136-143.
    Jablonkai I, Hatzios KK. (1993) In vitro conjugation of chloroacetanilide herbicides and atrazine with thiols and contribution of nonenzymatic conjugation to their glutathione-mediated metabolism in corn. J. Agric. Food Chem.41:1736-1742.
    Jepson I, Holt DC, Roussel V, Wright SY, Greenland AJ. (1997) Transgenic plant analysis as a tool for the study of maize glutathione S-transferases. In KK Hatzios, ed, Regulation of enzymatic systems detoxifying xenobiotics in plants. Kluwer Academic Publishers, Dordrecht, The Netherlands, pp:313-323.
    Joo JH, Bae YS, Lee JS. (2001) Role of auxin-induced reactive oxygen species in root gravitropism. Plant Physiol. 126:1055-1060.
    Kagale S, Divi U, Krochko J, Keller W, Krishna P. (2007) Brassinosteroid confers tolerance in Arabidopsis thaliana and Brassica napus to a range of abiotic stresses. Planta 225:353-364.
    KamimotoY, Hamamoto M, Shitan N, Yazaki K. (2009) Unusual expression of an Arabidopsis ATP-binding cassette transporter ABCC11. Plant Biotechnol.26: 261-265.
    Kasuga M, Miura S, Shinozaki K, Yamaguchi-Shinozaki K. (2004) A combination of the Arabidopsis drebla gene and stress-inducible rd29a promoter improved drought-and low-temperature stress tolerance in tobacco by gene transfer. Plant Cell Physiol. 45:346-350.
    Katsumi M. (1991) Physiological modes of brassinolide action in cucumber hypocotyls growth. In:Cutler HG, Yokata T, Adam G (eds.) Brassinosteroids Chemistry, Bioactivity and Applications. Washington DC, American Chemical Society.246-254.
    Kemmerling B, Schwedt A, Rodriguez P, Mazzotta S, Frank M, Qamar SA, Mengiste T, Betsuyaku S, Parker JE, Mussig C. (2007) The BRI1-associated kinase 1, BAK1, has a brassinolide-independent role in plant cell-death control. Curr. Biol. 17:1116-1122.
    Khripach V, Zhabinskii V, Groot AD. (2000) Twenty years of brassinosteroids: steroidal plant hormones warrant better crops for XXI century. Annual Botany 86: 441-447.
    Khripach VA, Zhabinskii VN, Litvinovskaya RP, Zavadskaya MI, Savel'eva EA, Karas Ⅱ, Kilcchevskii AV, Titova SN. (1996) A method for protection of potato from phytophthorosis. Pathological Application BY 960346
    Kim YM, Park K, Joo GJ, Jeong EM, Kim JE, Rhee IK. (2004) Glutathione-Dependent Biotransformation of the Fungicide Chlorothalonil. J. Agric. Food Chem.52:4192-4196.
    Krishna P. (2003) Brassinosteroid-mediated stress responses. J. Plant Growth Regul. 22:289-297.
    Kulaeva ON, Burkhanova EA, Fedina AB, Khokhlova VA, Bokebayeva GA, Vorbrodt HM, Adam G. (1991) Effect of brassinosteroids on protein synthesis and plant-cell ultrastructure under stress conditions. In:Cutler HG, Yokata T, Adam G (eds.) Brassinosteroids Chemistry, Bioactivity and Applications. Washington DC, American Chemical Society, pp:141-155.
    Kwak JM, Mori IC, Pei ZM, Leonhardt N, Torres MA, Dangl JL, Bloom RE, Bodde S, Jones JDG, Schroeder JI. (2003) NADPH oxidase AtrbohD and AtrbohF genes function in ROS-dependent ABA signaling in Arabidopsis. EMBO J.22: 2623-2633.
    Kwezi L, Meier S, Mungur L, Ruzvidzo O, Irving H, Gehring C. (2007) The Arabidopsis thaliana brassinosteroid receptor (AtBRI1) contains a domain that functions as a guanylyl cyclase in vitro. PLoS One 2:e449.
    Larsson A, Orrenius S, Holmgren A, Mannervik B. (1983) Functions of glutathione: biochemical, physiological, toxicological and clinical aspects. Raven Press, NewYork.
    Lenoir T, Giannella E. (2006) The emergence and diffusion of DNA microarray technology.J.Biomed. Discov. Collab.1:11-11.
    Li JM, Chory J. (1997) A putative leucine-rich repeat receptor kinase involed in brassinosteroid sigmal transduction. Cell 90:929-938.
    Li X. (2002) Analysis of food poisoning due to taking vegetable contaminated with organophosphorus pesticide. China Tropical Medicine 2:519-519.
    Liszkay A, Zalm E, Schopfer P. (2004) Production of reactive oxygen intermediates (O2·-, H2O2 and HO·) by maize roots and their role in wall loosening and elongation growth. Plant Physiol.136:3114-3123.
    Livak KJ, Schmittgen TD. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-△△CT method. Methods 25:402-408.
    Loos MA, Schlossera IF, Maphama WR. (1979) Phenoxy herbicide degradation in soils:Quantitative studies of 2,4-D-and MCPA-degrading microbial populations. Soil Bio. Biochem.11:377-385.
    Lundgren JG, Gassmann AJ, Bernal J, Duan JJ, Ruberson J. (2009) Ecological compatibility of GM crops and biological control. Crop protection 28: 1017-1030.
    Lynch LD, Ives AR, Waage JK, Hochberg ME, Thomas MB. (2002) The risks of biocontrol:transient impacts and minimum nontarget densities. Ecol. Appl.12: 1872-1882.
    Mandava NB. (1988) Plant growth-promoting brassinostcroids. Annu. Rev. Plant Biol. 39:23-52.
    Marrs KA. (1996) The functions and regulation of glutathione S-transferases in plants. Annu. Rev. Plant Biol.47:127-158.
    Martinoia E, Grill E, Tomasini R, Kreuz K, Amrehin N. (1993) ATP-dependent glutathione S-conjugate'export' pump in the vacuolar membrane of plants. Nature 364:247-249.
    McAinsh MR, Clayton H, Mansfield TA, Hetherington AM. (1996) Changes in stomatal behaviour and guard cell cytosolic free calcium in response to oxidative stress. Plant Physiol. 111:1031-1042.
    Meister A, Anderson ME. (1983) Glutathione. Annu. Rev Biochem.52:711-760.
    Meister A. (1994) Glutathione-ascorbic acid antioxidant system in animals. J. Biol. Chem.269:9397-9400.
    Meyer AJ, Fricker MD. (2002) Control of demand-driven biosynthesis of glutathione in green Arabidopsis suspension culture cells. Plant Physiol.130:1927-1937.
    Mitsou K, Koulianou A, Lambropoulou D, Pappas P, Albanis T, Lekka M. (2006) Growth rate effects, responses of antioxidant enzymes and metabolic fate of the herbicide Propanil in the aquatic plant Lemna minor. Chemosphere 62:275-284.
    Moore TC. (1989) Biochemistry and Physiology of Plant Hormone 2nd et.Springer-Verlag, New York, Heideberg, Berlin, pp.33
    Morant M, Schoch GA, Ullmann P, Ertunc T, Little D, Olsen CE, Petersen M, Negrel J, Werck-Reichhart D. (2007) Catalytic activity, duplication and evolution of the CYP98 cytochrome P450 family in wheat. Plant Mol. Biol.63:1-19.
    Morillon R, Catterou M, Sangwan RS, Sangwan BS, Lassalles JP. (2001) Brassinolide may control aquaporin activities in Arabidopsis thaliana. Planta 212:199-204.
    Mougin C, Cabanne F, Canivenc MC, Scalla R. (1990) Hydroxylation and N-demethylation of chlorotoluron by wheat microsomal enzymes. Plant Sci.66: 195-203.
    Mulbry W, Kearney PC. (1991) Degradation of Pesticides by microorganisms and the potential for genetic manipulation. Crop protection 10:334-346.
    Mulbry W, Karus J. (1989) Purification and characterization of three parathion hydrolase from gram negative baeterial strain. Appl. Environ Microbio.55: 289-294.
    Mussig C, Fischer S, Altmann T. (2002) Brassinosteroid-regulated gene expression. Plant Physiol.129:1241-1251.
    Nakashita H, Yasuda M, Nitta T, Asami T, Fujioka S, Arai Y, Sekimata K, Takatsuto S, Yamaguchi I, Yoshida S. (2003) Brassinosteroid functions in a broad range of disease resistance in tobacco and rice. Plant J.33:887-898.
    Naranjo SE, Ellsworth PC. (2009) Fifty years of the integrated control concept: moving the model and implementation forward in Arizona. Pest manag. Sci.65: 1267-1286.
    Neill SJ, Desikan R, Clarke A, Hurst RD, Hancock JT. (2002a) Hydrogen peroxide and nitric oxide as signaling molecules in plants. J. Exp. Bot.53:1237-1247.
    Neill SJ, Desikan R, Hancock J. (2002b) Hydrogen peroxide signaling. Curr. Opin. Plant Biol.5:388-395.
    Neuefeind T, Reinemer P, Bieseler B. (1997) Plant glutathione S-transferases and herbicide detoxification. Biol Chem 378:199-205.
    Ngowi AVF, Mbise TJ, Ijani ASM, London L, Ajayi OC. (2007) Smallholder vegetable farmers in Northern Tanzania:Pesticides use practices, perceptions, cost and health effects. Crop Protection 26:1617-1624.
    Obrigawitch TT, Cook G, Wetherington J. (1998) Assessment of effects on non-target plants from sulfonylurea herbicides using field approaches. Pestic. Sci.52: 199-217.
    Ogweno JO, Song XS, Shi K, Hu WH, Mao WH, Zhou YH, Yu JQ. (2008)
    Brassinosteroids alleviate heat-induced inhibition of photosynthesis by increasing carboxylation efficiency and enhancing antioxidant systems in Lycopersicon esculentum. J. Plant Growth Regul.27:49-57.
    Ohkawa H, Imaishi H, Shiota N, Yamada T, Inui H. (1999) Cytochrome P450s and Other Xenobiotic Metabolizing Enzymes in Plants, Vol 233. The Royal Society of Chemistry, Cambridge, UK.
    Orozco-Cardenas M, Ryan CA. (1999) Hydrogen peroxide is generated systemically in plant leaves by wounding and systemin via the octadecanoid pathway. Proc. Natl. Acad. Sci. USA 96:6553-6557.
    Orozco-Cardenas ML, Narvaez-Vasquez J, Ryan CA. (2001) Hydrogen peroxide acts as a second messenger for the induction of defense genes in tomato plants in response to wounding, systemin, and methyl jasmonate. Plant Cell 13:179-191.
    Pimental D, Levitan L. (1986) Pesticides:amounts applied and amounts reaching pests. Biosciences 36:86-91.
    Pimentel D. (2005) Environmental and economic costs of the application of pesticides primarily in the United States. Environ. Dev. Sustainabil.7:229-252.
    Prasad TK, Anderson MD, Martin BA, Stewart CR. (1994) Evidence for chilling-induced oxidative stress in maize seedlings and a regulatory role for hydrogen peroxide. Plant Cell 6:65-74.
    Pustovoitova TN, Zhdanova NE, Zholkevich VN. (2001) Epibrassinolide increases plant drought resistance. Doklady Biochemistry and Biophysics 376:36-38.
    Radosevich M, Traina SJ, Tuovinen OH. (1996) Biodegradation of atrazine in surface soils and subsurface sediments collected from an agricultural research farm. Biodegradation 7:137-149.
    Rea PA. (1999) MRP subfamily ABC transporters from plants and yeast. J. Exp. Bot. 50:895-913.
    Rea PA. (2007) Plant ATP-binding cassette transporter. Annu. Rev. Plant Biol.58: 347-375.
    Rea PA, Li ZS, Lu YP, Drozdowicz YM, Martinoia E. (1998) From vacuolar GS-X pumps to multispecific ABC transporters. Annu. Rev. Plant Biol.49:725-760.
    Rebhan M, Chalifa-Caspi V, Prilusky J, Lancet D. (1998) GeneCards:a novel functional genomics compendium with automated data mining and query reformulation support. Bioinformatics 14:656-664.
    Robineau T, Batard Y, Nedelkina S, Cabello-Hurtado F, LeRet M, Sorokine 0, Didierjean L, Werck-Reichhart D. (1998) The chemically inducible plant cytochrome P450 CYP76B1 actively metabolizes phenylureas and other xenobiotics. Plant Physiol.118:1049-1056.
    Romano ML, Stephenson GR, Tal A, Hall JC. (1993) The effect of monooxygenase and glutathione S-transferase inhibitors on the metabolism of diclofop-methyl and fenoxaprop-ethyl in barley and wheat. Pestic. Biochem. Physiol.46: 181-189.
    Romantschuk M, Sarand I, Petanen T, Peltola R, Jonsson-Vihanne M, Koivula T. (2000) Means to improve the effect of in situ bioremediation of contaminated soil:an overview of novel approaches. Environ. Pollut.107:179-185.
    Rouhier N, Lemaire SD, Jacquot JP. (2008) The role of glutathione in photosynthetic organisms:emerging functions for glutaredoxins and glutathionylation. Annu. Rev. Plant Biol.59:143-166.
    Rozman KK, Klaassen CD. (1996) Absorption, distribution, and excretion of toxicants. Pages 177-183 in L. Casarett and J. Doull, eds. Toxicology:The Basic Science of Poisons. New York:McGraw-Hill Health Professions Division.
    Rushmore TH, Pickett CB. (1993) Glutathione S-transferases, structure, regulation, and therapeutic implications. J. Biol. Chem.268:11475-11478.
    Saladin G, Clement C. (2005) Physiological effects of pesticides on cultivated crops. In Agriculture and Soil Pollution:New Research, Livingston, J. V., Ed.; Nova Science Publishers:Hauppauge, NY, pp 53-86.
    Sandermann H. (1994) Higher-plant metabolism of xenobiotics:the green liver concept. Pharmacogenetics 4:225-241.
    Sasabe M, Wen ZM, Berenbaum MR, Schuler MA. (2004) Molecular analysis of CYP321A1, a novel cytochrome P450 involved in metabolism of plant allelochernicals (furanocoumarins) and insecticides (cypermethrin) in Helicoverpa zea. Gene 338:163-175.
    Sasse JM. (1997) Recent progress in brassinosteroid research. Plant Physiol.100: 696-701.
    Schardein JL, Scialli AR. (1999) The legislation of toxicologic safety factors:the quality protection act with chlorpyrifos as a test case. Reprod. Toxicol.13:1-14.
    Schopfer P, Liszkay A, Bechtold M, Frahry G, Wagner A. (2002) Evidence that hydroxyl radicals mediate auxin-induced extension growth. Planta 214:821-828.
    Sgherri CLM, Navari-Izzo F. (1995) Sunflower seedling subjected to increasing water deficit stress:oxidative stress and defense mechanisms. Physiol. Plant.93: 25-30.
    Shimabukuro RH, Frear DS, Swanson HR, Walsh WC. (1971) Glutathione conjugation:an enzymatic basis for atrazine resistance in corn. Plant Physiol.47: 10-14.
    Shimabukuro RH, Swanson HR, Walsh WC. (1970) Glutathione conjugation:atrazine detoxification mechanism in corn. Plant Physiol.46:103-107.
    Shiota N, Inui H, Okhawa H. (1996) Metabolism of the herbicide chlortoluron in transgenic tobacco plants expressing the fused enzyme between rat cytochrome P4501A1 and yeast NADPH-cytochrome P450 oxidoreductase. Pestic. Biochem. Physiol.54:190-198.
    Sies H, Wahllander A, Waydhas C, Soboll S, Haberle D. (1980) Functions of intracellular glutathione in hepatic hydroperoxide and drug metabolism and the role of extracellular glutathione. Adv. Enzyme Regul.18:303-320.
    Siminszky B, Corbin FT, Ward ER, Fleischmann TJ, Dewey RE. (1999) Expression of a soybean cytochrome P450 monooxygenase cDNA in yeast and tobacco enhances the metabolism of phenylurea herbicides. Proc. Natl. Acad. Sci. USA 96:1750-1755.
    Singh I, Shono M. (2005) Physiological and molecular effects of 24-epibrassinolide, a brassinosteroid on thermotolerance of tomato. Plant Growth Regul.47:111-119.
    Statistics bureau and the director-general for policy planning (Statistical standards) and statistical research and training institute of ministry of internal affairs and
    communications of Japan. (2008) Statistic of the World 2008. Statistics Bureau Press.
    Sunkar R, Kapoor A, Zhu JK. (2006) Posttranscriptional induction of two Cu/Zn superoxide dismutase Genes in Arabidopsis is mediated by downregulation of miR398 and important for oxidative stress tolerance. Plant Cell 18:2051-2065.
    Symondson WOC, Suderland KD, Greenstone MH. (2002) Can the generalist predators be effective biocontrol agents? Ann. Rev. Entomol.47:561-594.
    Tal JA, Hall JC, Stephenson GR. (1995) Non-enzymatic conjugation of fenoxaprop-ethyl with glutathione and cysteine in several grass species. Weed Res.35:133-139.
    Tang J, Cao Y, Rose RL, Brimfield AA, Dai D, Goldstein JA, Hodgson E. (2001) Metabolism of chlorpyrifos by human cytochrome P450 isoforms and human, mouse, and rat liver microsomes. Drug metabolism and disposition 29: 1201-1204.
    Tang W, Deng Z, Wang ZY. (2010) Proteomics shed light on the brassinosteroid signaling mechanisms. Curr. Opin. Plant Biol.13:27-33.
    Tarca AL, Romero R, Draghici S. (2006) Analysis of microarray experiments of gene expression profiling. Am. J. Obstet. Gynecol.195:373-388.
    Tegtmeier EM, Duffy MD. (2004) External costs of agricultural production in the United States. Int. J. Agric. Sustainabil.2:1-20.
    Theodoulou F, Clark IM, Pellett KE, Hallahan DL. (1998) A herbicide safener-induced MRP homologue from wheet. In 11 th international workshop on plant membrane biology, Cambridge, UK,9-14.
    Thordal-Christensen H, Zhang Z, Wei Y, Collinge DB. (1997) Subcellular localization of H2O2 in plants:H2O2 accumulation in papillae and hypersensitive response during the barley-powdery mildew interaction. Plant J.11:1187-1194.
    Tilman D, Fargione J, Wolff B, D'Antonio C, Dobson A, Howarth R, Schindler D, Schlesinger WH, Simberloff D, Swackhamer D. (2000) Forecasting Agriculturally Driven Global Environmental Change. Science 292:281-284.
    Timmis KN, Pieper DH. (1999) Bacteria designed for bioremediation. Trends Biotechnol 17:201-204.
    Torres MA, Dangl JL. (2005) Functions of the respiratory burst oxidase in biotic interactions, abiotic stress and development. Curr. Opin. Plant Biol.8:397-403.
    Torres MA, Jones JDG, Dangl JL. (2005) Pathogen-induced, NADPH oxidase-derived reactive oxygen intermediates suppress stress spread of cell death in Arabidopsis thaliana. Nat. Genet.37:1130-1134.
    Trevno V, Falciani F, Barrera-Saldana HA. (2007) DNA microarray:a powerful genomic tool for biomedical and clinical research. Mol. Med.13:527-541.
    Tsuchida, S. and K. Sato. (1992) Glutathione transferases and cancer. CRC Crit. Rev. Biochem. Mol. Biol.27:337-384.
    Untiedt R, Blanke MM. (2004) Effects of fungicide and insecticide mixtures on apple tree canopy photosynthesis, dark respiration and carbon economy. Crop Prot.23: 1001-1006.
    Van Eerd LL, Hoagland RE, Zablotowicz RM, Hall JC. (2003) Pesticide metabolism in plants and microorganisms. Weed Sci.51:472-495.
    Vardhini BV, Rao SSR. (2003) Amelioration of osmotic stress by brassinosteroids on seed germination and seedling growth of three varieties of sorghum. Plant Growth Regul.41:25-31.
    Vardhini VB, Rao SSR. (1998) Effect of brassinosteroids on growth, metabolite content and yield of Arachis Hypogaea. Phytochemistry 48:927-930.
    Vincent PG, Sisler HD. (1968) Mechanism of antifungal action of 2,4,5,6-tetrachloroisophtalonitrile. Plant Physiol.21:1249-1264.
    Ward OP, Singh A. (2004) Soil bioremediation and phytoremediation-An overview. Soil biology 1:1-12.
    Wheeler WB. (2002) Pesticide in agriculture and environment, Mareel Dekker, New York.
    Wheelock CE, Shan G, Ottea J. (2005) Overview of carboxylesterases and their role in the metabolism of insecticides. J. Pesticide Sci.30:75-83.
    Xia XJ, Huang YY, Wang L, Zhou YH, Yu JQ. (2006) Pesticides-induced depression of photosynthesis was alleviated by 24-epibrassinolide pretreatment in Cucumis sativus L. Pest. Biochem. Physiol.86:42-48.
    Xia XJ, Wang YJ, Zhou YH, Tao Y, Mao WH, Shi K, Asami T, Chen ZX, Yu JQ. (2009) Reactive oxygen species are involved in brassinosteroid-induced stress tolerance in Cucumber. Plant Physiol.150:801-814.
    Yamada T, Kambara Y, Imaishi H, Ohkawa H. (2000) Molecular cloning of novel cytochrome P450 species induced by chemical treatments in cultured tobacoo cells. Pest. Biochem. Physiol.68:11-25.
    Yoshioka H, Numata N, Nakajima K, Katou S, Kawakita K, Rowland O, Jones JDG, Doke N. (2003) Nicotiana benthamiana gp91phox homologs NbrbohA and NbrbohB participate in H2O2 accumulation and resistance to Phytophthora infestans. Plant Cell 15:706-718.
    Yu BP. (1994) Cellular defenses against damage from reactive oxygen species. Pharmacol. Rev.74:139-162.
    Yu JQ, Huang LF, Hu WH, Zhou YH, Mao WH, Ye SF, Nogues S. (2004) A role for brassinosteroids in the regulation of photosynthesis in Cucumis sativus. J. Exp. Bot.55:1135-1143.
    Zhang J, Lan W, Qiao C, Jiang H, Mulchandani A, Chen W. (2004) Bioremediation of organophosphorus pesticides by surface-expressed carboxylesterase from mosquito on Escherichia coli.Biotechnol. Prog.20:1567-1571.
    Zhang JL, Qiao CL. (2002) Novel approaches for remediation of pesticide pollutants. Int. J. Environ. Pollut.18:423-433.
    Zhang X, Zhang L, Dong F, Gao J, Galbraith DW, Song C. (2001) Hydrogen peroxide is involved in abscisic acid-induced stomatal closure in Vicia faba. Plant Physiol. 126:1438-1448.

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