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Melatonin ameliorates myocardial ischemia reperfusion injury through SIRT3-dependent regulation of oxidative stress and apoptosis.
- Source :
- Journal of Pineal Research; Sep2017, Vol. 63 Issue 2, pn/a-N.PAG, 18p
- Publication Year :
- 2017
-
Abstract
- Sirtuins are a family of highly evolutionarily conserved nicotinamide adenine nucleotide-dependent histone deacetylases. Sirtuin-3 ( SIRT3) is a member of the sirtuin family that is localized primarily to the mitochondria and protects against oxidative stress-related diseases, including myocardial ischemia/reperfusion ( MI/R) injury. Melatonin has a favorable effect in ameliorating MI/R injury. We hypothesized that melatonin protects against MI/R injury by activating the SIRT3 signaling pathway. In this study, mice were pretreated with or without a selective SIRT3 inhibitor and then subjected to MI/R operation. Melatonin was administered intraperitoneally (20 mg/kg) 10 minutes before reperfusion. Melatonin treatment improved postischemic cardiac contractile function, decreased infarct size, diminished lactate dehydrogenase release, reduced the apoptotic index, and ameliorated oxidative damage. Notably, MI/R induced a significant decrease in myocardial SIRT3 expression and activity, whereas the melatonin treatment upregulated SIRT3 expression and activity, and thus decreased the acetylation of superoxide dismutase 2 ( SOD2). In addition, melatonin increased Bcl-2 expression and decreased Bax, Caspase-3, and cleaved Caspase-3 levels in response to MI/R. However, the cardioprotective effects of melatonin were largely abolished by the selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl)pyridine (3- TYP), suggesting that SIRT3 plays an essential role in mediating the cardioprotective effects of melatonin. In vitro studies confirmed that melatonin also protected H9c2 cells against simulated ischemia/reperfusion injury ( SIR) by attenuating oxidative stress and apoptosis, while SIRT3-targeted si RNA diminished these effects. Taken together, our results demonstrate for the first time that melatonin treatment ameliorates MI/R injury by reducing oxidative stress and apoptosis via activating the SIRT3 signaling pathway. [ABSTRACT FROM AUTHOR]
- Subjects :
- MELATONIN
CORONARY disease
REPERFUSION injury
APOPTOSIS
OXIDATIVE stress
Subjects
Details
- Language :
- English
- ISSN :
- 07423098
- Volume :
- 63
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Journal of Pineal Research
- Publication Type :
- Academic Journal
- Accession number :
- 124433170
- Full Text :
- https://doi.org/10.1111/jpi.12419