Cardiac Fas-Dependent and Mitochondria-Dependent Apoptotic Pathways in a Transgenic Mouse Model of Huntington's Disease

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• 作者：Bor-Tsang Wu ; Ming-Chang Chiang ; Ching-Yi Tasi ; Chia-Hua Kuo…
• 关键词：Apoptosis ; Caspase ; Heart ; Huntington’s disease
• 刊名：Cardiovascular Toxicology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：16
• 期：2
• 页码：111-121
• 全文大小：1,430 KB
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• 作者单位：Bor-Tsang Wu (1)
  Ming-Chang Chiang (2)
  Ching-Yi Tasi (1)
  Chia-Hua Kuo (3)
  Woei-Cherng Shyu (4) (5) (6)
  Chung-Lan Kao (7) (8)
  Chih-Yang Huang (10) (11) (9)
  Shin-Da Lee (1) (12)
  
  1. Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan
  2. Department of Life Science, Fu Jen Catholic University, New Taipei City, 242, Taiwan
  3. Laboratory of Exercise Biochemistry, Taipei Physical Education College, Taipei, Taiwan
  4. Translational Medicine Research Center, China Medical University Hospital, Taichung, 40447, Taiwan
  5. Graduate Institute of Immunology, China Medical University, Taichung, 40202, Taiwan
  6. Department of Neurology, Center for Neuropsychiatry, China Medical University Hospital, Taichung, 40447, Taiwan
  7. Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan
  8. School of Medicine, National Yang-Ming University, Taipei, Taiwan
  10. Institute of Medical Science, China Medical University, Taichung, 40402, Taiwan
  11. Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan
  9. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, 40202, Taiwan
  12. Department of Healthcare Administration, Asia University, Taichung, 41354, Taiwan
  
• 刊物主题：Pharmacology/Toxicology; Cardiology;
• 出版者：Springer US
• ISSN：1559-0259

文摘

Huntington’s disease is an autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the huntingtin gene. Heart disease is the second leading cause of death in patients with Huntington’s disease. This study was to evaluate whether cardiac Fas-dependent and mitochondria-dependent apoptotic pathways are activated in transgenic mice with Huntington’s disease. Sixteen Huntington’s disease transgenic mice (HD) and sixteen wild-type (WT) littermates were studied at 10.5 weeks of age. The cardiac characteristics, myocardial architecture, and two major apoptotic pathways in the excised left ventricle from mice were measured by histopathological analysis, Western blotting, and TUNEL assays. The whole heart weight and the left ventricular weight decreased significantly in the HD group, as compared to the WT group. Abnormal myocardial architecture, enlarged interstitial spaces, and more cardiac TUNEL-positive cells were observed in the HD group. The key components of Fas-dependent apoptosis (TNF-alpha, TNFR1, Fas ligand, Fas death receptors, FADD, activated caspase-8, and activated caspase-3) and the key components of mitochondria-dependent apoptosis (Bax, Bax-to-Bcl-2 ratio, cytosolic cytochrome c, activated caspase-9, and activated caspase-3) increased significantly in the hearts of the HD group. Cardiac Fas-dependent and mitochondria-dependent apoptotic pathways were activated in transgenic mice with Huntington’s disease, which might provide one of possible mechanisms to explain why patients with Huntington’s disease will develop heart failure.