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

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)697-705
Number of pages9
JournalJournal of Cellular Biochemistry
Volume107
Issue number4
DOIs
Publication statusPublished - Jul 1 2009
Externally publishedYes

Fingerprint

Grape Seed Extract
Reperfusion Injury
Cardiac Myocytes
Nitric Oxide Synthase
Nitric Oxide
Reperfusion
NG-Nitroarginine Methyl Ester
Ischemia
Grape Seed Proanthocyanidins
Reactive Oxygen Species
Arginine
Phosphorylation

Keywords

  • Akt
  • Cardiomyocytes
  • Grape seed proanthocyanidin extract
  • Ischemia/reperfusion injury
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Shao, Z. H., Wojcik, K. R., Dossumbekova, A., Hsu, C., Mehendale, S. R., Li, C. Q., ... Vanden Hoek, T. L. (2009). Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion injury via Akt-NOS signaling. Journal of Cellular Biochemistry, 107(4), 697-705. https://doi.org/10.1002/jcb.22170

Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion injury via Akt-NOS signaling. / Shao, Zuo Hui; Wojcik, Kimberly R.; Dossumbekova, Anar; Hsu, Chinwang; Mehendale, Sangeeta R.; Li, Chang Qing; Qin, Yimin; Sharp, Willard W.; Chang, Wei Tien; Hamann, Kimm J.; Yuan, Chun Su; Vanden Hoek, Terry L.

In: Journal of Cellular Biochemistry, Vol. 107, No. 4, 01.07.2009, p. 697-705.

Research output: Contribution to journalArticle

Shao, ZH, Wojcik, KR, Dossumbekova, A, Hsu, C, Mehendale, SR, Li, CQ, Qin, Y, Sharp, WW, Chang, WT, Hamann, KJ, Yuan, CS & Vanden Hoek, TL 2009, 'Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion injury via Akt-NOS signaling', Journal of Cellular Biochemistry, vol. 107, no. 4, pp. 697-705. https://doi.org/10.1002/jcb.22170
Shao, Zuo Hui ; Wojcik, Kimberly R. ; Dossumbekova, Anar ; Hsu, Chinwang ; Mehendale, Sangeeta R. ; Li, Chang Qing ; Qin, Yimin ; Sharp, Willard W. ; Chang, Wei Tien ; Hamann, Kimm J. ; Yuan, Chun Su ; Vanden Hoek, Terry L. / Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion injury via Akt-NOS signaling. In: Journal of Cellular Biochemistry. 2009 ; Vol. 107, No. 4. pp. 697-705.
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