Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion injury via Akt-NOS signaling

Zuo Hui Shao, Kimberly R. Wojcik, Anar Dossumbekova, Chinwang Hsu, Sangeeta R. Mehendale, Chang Qing Li, Yimin Qin, Willard W. Sharp, Wei Tien Chang, Kimm J. Hamann, Chun Su Yuan, Terry L. Vanden Hoek

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49 引文 斯高帕斯(Scopus)

摘要

Ischemia/reperfusion (I/R) injury in cardiomyocytes is related to excess reactive oxygen species (ROS) generation and can be modulated by nitric oxide (NO). We have previously shown that grape seed proanthocyanidin extract (GSPE), a naturally occurring antioxidant, decreased ROS and may potentially stimulate NO production. In this study, we investigated whether GSPE administration at reperfusion was associated with cardioprotection and enhanced NO production in a cardiomyocyte I/R model. GSPE attenuated I/R-induced cell death [18.0 ± 1.8% (GSPE, 50 μg/ml) vs. 42.3 ± 3.0% (I/R control), P < 0.001], restored contractility (6/6 vs. 0/6, respectively), and increased NO release. The NO synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 200 μM) significantly reduced GSPE-induced NO release and its associated cardioprotection [32.7 ± 2.7% (GSPE + L-NAME) vs. 18.0 ± 1.8% (GSPE alone), P < 0.01]. To determine whether GSPE induced NO production was mediated by the Akt-eNOS pathway, we utilized the Akt inhibitor API-2. API-2 (10 μM) abrogated GSPE-induced protection [44.3% ± 2.2% (GSPE + API-2) vs. 27.0% ± 4.3% (GSPE alone), P < 0.01], attenuated the enhanced phosphorylation of Akt at Ser473 in GSPE-treated cells and attenuated GSPE-induced NO increases. Simultaneously blocking NOS activation (L-NAME) and Akt (API-2) resulted in decreased NO levels similar to using each inhibitor independently. These data suggest that in the context of GSPE stimulation, Akt may help activate eNOS, leading to protective levels of NO. GSPE offers an alternative approach to therapeutic cardioprotection against I/R injury and may offer unique opportunities to improve cardiovascular health by enhancing NO production and increasing Akt-eNOS signaling.

原文英語
頁(從 - 到)697-705
頁數9
期刊Journal of Cellular Biochemistry
107
發行號4
DOIs
出版狀態已發佈 - 七月 1 2009

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 細胞生物學

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