Resveratrol protects cardiomyocytes from hypoxia-induced apoptosis through the SIRT1-FoxO1 pathway.
Loss of cardiomyocytes through apoptosis has been proposed as a cause of ventricular remodeling and heart failure. Ischemia- and hypoxia-induced apoptosis of cardiomyocytes reportedly plays an important role in many cardiac pathologies. We investigated whether resveratrol (Res) has direct cytoprotective effects against ischemia/hypoxia for cardiomyocytes. Exposure of H9c2 embryonic rat heart-derived cells to hypoxia for 24h caused a significant increase in apoptosis, as evaluated by TUNEL and flow cytometry, while treatment with 20 microM Res greatly decreased hypoxia-induced apoptosis in these cells. Exposure of the cells to Res (20 microM) caused rapid activation of SIRT1, which had a dual effect on FoxO1 function: SIRT1 increased FoxO1's ability to induce cell cycle arrest, but inhibited FoxO1's ability to induce cell death. This effect could be reversed by SIRT1 inhibition. Results of our study indicate that Res inhibits hypoxia-induced apoptosis via the SIRT1-FoxO1 pathway in H9c2 cells. This polyphenol may have potential in preventing cardiovascular disease, especially in coronary artery disease (CAD) patients.
Chen
Chun-Juan
CJ
Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.
Yu
Wei
W
Fu
Yu-Cai
YC
Wang
Xin
X
Li
Ji-Lin
JL
Wang
Wei
W
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D051858:Forkhead Transcription Factors / Q000378:metabolism; D017202:Myocardial Ischemia / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D000077185:Resveratrol; D056564:Sirtuin 1; D037761:Sirtuins / Q000819:agonists / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D000071161:Forkhead Box Protein O1
D000975:Antioxidants; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D000077185:Resveratrol; D056564:Sirtuin 1; D037761:Sirtuins; D013267:Stilbenes; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C488368:Sirt1 protein, rat