Resveratrol attenuates myocardial hypoxia/reoxygenation-induced cell apoptosis through DJ-1-mediated SIRT1-p53 pathway
Resveratrol, a multi-functional phytoalexin, has been well indicated to exert cardioprotective effects by weakening ischemia/reperfusion (I/R) injury, and cell apoptosis is a vital way in I/R injury. SIRT1-p53 pathway has strong significance in regulating cell apoptosis. DJ-1 can directly bind to SI...
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Veröffentlicht in: | Biochemical and biophysical research communications 2019-06, Vol.514 (2), p.401-406 |
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Sprache: | eng |
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Zusammenfassung: | Resveratrol, a multi-functional phytoalexin, has been well indicated to exert cardioprotective effects by weakening ischemia/reperfusion (I/R) injury, and cell apoptosis is a vital way in I/R injury. SIRT1-p53 pathway has strong significance in regulating cell apoptosis. DJ-1 can directly bind to SIRT1 and stimulate the activity of SIRT1-p53. Therefore, the current study was determined whether Resveratrol attenuates hypoxia/reoxygenation (H/R)-induced cell apoptosis, and whether DJ-1-mediated SIRT1 activation involves in the cardioprotective effects of Resveratrol. The results showed that remarkable decrease in the number of apoptotic cells along with reduction of lactate dehydrogenase release and restoration of cell viability emerged when Resveratrol was applied in the H9c2 cells exposed to H/R. Moreover, Resveratrol increased DJ-1 expression and promoted the interaction of DJ-1 with SIRT1, which further contributed to subsequent restoration of SIRT1 activity and decrease of acetylation level of p53. However, above cardioprotective effects of Resveratrol were abrogated by DJ-1 siRNA and SIRT1 specific inhibitor Sirtinol. In conclusion, the current study demonstrated that Resveratrol suppressed H/R-induced cell apoptosis, which may be conducted by up-regulating DJ-1, and later activating SIRT1 activity and subsequently inhibiting p53 acetylation level in the H9c2 cells.
•Resveratrol increased the DJ-1 expression and promoted the interaction of DJ-1 with SIRT1 in the H9c2 cells exposed to H/R.•Resveratrol restored SIRT1 activity in a way of DJ-1-dependence in the H9c2 cells exposed to H/R.•Resveratrol decreased H/R-induced p53 acetylation level by DJ-1-mediated SIRT1 activation in the H9c2 cells.•Resveratrol attenuated H/R-induced cell apoptosis by DJ-1-mediated SIRT1 activation in the H9c2 cells. |
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ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/j.bbrc.2019.04.165 |