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% O-2, 1 mo), rats with chronic intermittent hypoxia exposure (Hypoxia, 3-7% O-2 vs. 21% O-2 per 40 s cycle, 8 h per day, 1 mo), and rats with pretreatment of the superoxide anion scavenger and chronic intermittent hypoxia exposure (Hypoxia-O-2(-)-Scavenger, MnTMPyP pentachloride, 1 mg/kg ip per day; 3-7% O-2 vs. 21% O-2 per 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.
[1]China Med Univ, Grad Inst Clin Med Sci, Taichung, Taiwan.
[2]China Med Univ Hosp, Dept Internal Med, Div Cardiol, Taichung, Taiwan.
[3]Tzu Chi Univ, Dept Physiol, Hualien, Taiwan.
[4]China Med Univ Hosp, Clin Immunol Ctr, Taichung, Taiwan.
[5]China Med Univ, Grad Inst Chinese Med Sci, Taichung, Taiwan.
[6]China Med Univ, Inst Basic Med Sci, Taichung, Taiwan.
[7]Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung, Taiwan.
[8]Shanghai Univ Tradit Chinese Med, Sch Rehabil Sci, Shanghai, Peoples R China.
[9]Asia Univ, Dept Occupat Therapy, Taichung, Taiwan.
[10]China Med Univ, Grad Inst Rehabil Sci, Dept Phys Therapy, Taichung, Taiwan.
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