title: Effect of superoxide anion scavenger on rat hearts with chronic intermittent hypoxia.
abstract: Only very limited information regarding the protective effects of the superoxide anion scavenger on chronic intermittent hypoxia-induced cardiac apoptosis is available. The purpose of this study is to evaluate the effects of the superoxide anion scavenger on cardiac apoptotic and prosurvival pathways in rats with sleep apnea. Forty-two Sprague-Dawley rats were divided into three groups, rats with normoxic exposure (Control, 21% O2, 1 mo), rats with chronic intermittent hypoxia exposure (Hypoxia, 3-7% O2vs. 21% O2per 40 s cycle, 8 h per day, 1 mo), and rats with pretreatment of the superoxide anion scavenger and chronic intermittent hypoxia exposure (Hypoxia-O2 (-)-Scavenger, MnTMPyP pentachloride, 1 mg/kg ip per day; 3-7% O2vs. 21% O2per 40 s cycle, 8 h per day, 1 mo) at 5-6 mo of age. After 1 mo, the protein levels and apoptotic cells of excised hearts from three groups were measured by Western blotting and terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay. The superoxide anion scavenger decreased hypoxia-induced myocardial architecture abnormalities, left ventricular hypertrophy, and TUNEL-positive apoptosis. The superoxide anion scavenger decreased hypoxia-induced Fas ligand, Fas death receptors, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas-dependent apoptotic pathway) as well as Bad, activated caspase-9 and activated caspase-3 (mitochondria-dependent apoptotic pathway), endonuclease G (EndoG), apoptosis-inducing factor (AIF), and TUNEL-positive apoptosis. The superoxide anion scavenger increased IGF-1, IGF-1R, p-PI3k, p-Akt, p-Bad, Bcl-2, and Bcl-xL (survival pathway). Our findings imply that the superoxide anion scavenger might prevent cardiac Fas-mediated and mitochondrial-mediated apoptosis and enhance the IGF-1-related survival pathway in chronic intermittent hypoxia. The superoxide anion scavenger may prevent chronic sleep apnea-enhanced cardiac apoptotic pathways and enhances cardiac survival pathways.
authors.affiliation: China Medical University, Graduate Institute of Clinical Medical Science, Taichung, Taiwan; Division of Cardiology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan;
authors.forename: Peiying
authors.initials: P
authors.lastname: Pai
authors.affiliation: Department of Physiology, Tzu Chi University, Hualien, Taiwan;
authors.forename: Ching Jung
authors.initials: CJ
authors.lastname: Lai
authors.affiliation: China Medical University, Graduate Institute of Clinical Medical Science, Taichung, Taiwan; Clinical Immunology Center, China Medical University Hospital, Taichung, Taiwan;
authors.forename: Ching-Yuang
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan;
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Liou
authors.affiliation: Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan; Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan;
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.affiliation: School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Occupational Therapy, Asia University, Taichung, Taiwan; and Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan shinda@mail.cmu.edu.tw.
authors.forename: Shin-Da
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D012891:Sleep Apnea Syndromes / Q000378:metabolism / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; D019014:fas Receptor; D013481:Superoxides; D007334:Insulin-Like Growth Factor I; D020169:Caspases
keywords: Fas receptor; caspase; cell death; heart; hypoxia; survival