651. Hydrogen sulfide protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis by preventing GSK-3beta-dependent opening of mPTP
- Author
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Yong-Gang Wang, Yi-Chun Zhu, Cai-Cai Zhang, Ling-Ling Yao, Yin-Xiang Cao, and Xiao-Wei Huang
- Subjects
Male ,Physiology ,Hydrogen sulfide ,Blotting, Western ,Apoptosis ,Protective Agents ,Transfection ,Mitochondrial Membrane Transport Proteins ,Mitochondria, Heart ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Glycogen Synthase Kinase 3 ,Physiology (medical) ,medicine ,In Situ Nick-End Labeling ,Myocyte ,Animals ,Myocytes, Cardiac ,Hydrogen Sulfide ,Phosphorylation ,GSK3B ,bcl-2-Associated X Protein ,Cardioprotection ,Glycogen Synthase Kinase 3 beta ,Chemistry ,Caspase 3 ,Mitochondrial Permeability Transition Pore ,MPTP ,Myocardium ,Hypoxia (medical) ,Caspase Inhibitors ,Cell Hypoxia ,Cell biology ,Rats ,Mitochondrial permeability transition pore ,Biochemistry ,Calcium ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Plasmids - Abstract
Hydrogen sulfide (H2S) is an endogenously generated gaseous transmitter, which has recently been suggested to regulate cardiovascular functions. The present study aims to clarify the mechanisms underlying the cardioprotective effects of H2S. Signaling elements were examined in cardiomyocytes cultured under hypoxia/reoxygenation conditions and in a rat model of ischemia-reperfusion. In cultured cardiomyocytes, sodium hydrosulfide (NaHS; 10, 30, and 50 μmol/l) showed concentration-dependent inhibitory effects on cardiomyocyte apoptosis induced by hypoxia/reoxygenation. These effects were associated with an increase in phosphorylation of glycogen synthase kinase-3β (GSK-3β) (Ser9) and a decrease in Bax translocation, caspase-3 activation, and mitochondrial permeability transition pore (mPTP) opening. Transfection of a phosphorylation-resistant mutant of GSK-3β at Ser9 attenuated the effects of NaHS in reducing cardiomyocyte apoptosis, Bax translocation, caspase-3 activation, and mPTP opening. In a rat model of ischemia-reperfusion, NaHS administration reduced myocardial infarct size and increased the phosphorylation of GSK-3β (Ser9) at a dose of 30 μmol/kg. In conclusion, the H2S donor prevents cardiomyocyte apoptosis by inducing phosphorylation of GSK-3β (Ser9) and subsequent inhibition of mPTP opening.
- Published
- 2010