title: Cardiac Fas-Dependent and Mitochondria-Dependent Apoptotic Pathways in a Transgenic Mouse Model of Huntington's Disease.
abstract: 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.
authors: Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan.
authors: Bor-Tsang
authors: BT
authors: Wu
authors: Department of Life Science, Fu Jen Catholic University, New Taipei City, 242, Taiwan.
authors: Ming-Chang
authors: MC
authors: Chiang
authors: Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan.
authors: Ching-Yi
authors: CY
authors: Tasi
authors: Laboratory of Exercise Biochemistry, Taipei Physical Education College, Taipei, Taiwan.
authors: Chia-Hua
authors: CH
authors: Kuo
authors: Translational Medicine Research Center, China Medical University Hospital, Taichung, 40447, Taiwan.|Graduate Institute of Immunology, China Medical University, Taichung, 40202, Taiwan.|Department of Neurology, Center for Neuropsychiatry, China Medical University Hospital, Taichung, 40447, Taiwan.
authors: Woei-Cherng
authors: WC
authors: Shyu
authors: Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Chung-Lan
authors: CL
authors: Kao
authors: Graduate Institute of Chinese Medical Science, China Medical University, Taichung, 40202, Taiwan.|Institute of Medical Science, China Medical University, Taichung, 40402, Taiwan.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan.
authors: Chih-Yang
authors: CY
authors: Huang
authors: Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan. shinda@mail.cmu.edu.tw.|Department of Healthcare Administration, Asia University, Taichung, 41354, Taiwan. shinda@mail.cmu.edu.tw.
authors: Shin-Da
authors: SD
authors: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism*
chemical_list: C491899:Fas protein, mouse; D019014:fas Receptor
keywords: Apoptosis; Caspase; Heart; Huntington’s disease