期刊
JOURNAL OF PINEAL RESEARCH
卷 58, 期 1, 页码 61-70出版社
WILEY
DOI: 10.1111/jpi.12193
关键词
cerebral-protection; ischemia reperfusion; melatonin; mitochondrial dysfunction; SIRT1 signaling
资金
- National Natural Science Foundation of China [81070951, 81222015, 81000938, 81170213, 81102091]
- Excellent Doctoral Support Project of the Fourth Military Medical University [2013D01]
- New Century Talent Supporting Project by Chinese Education Ministry [NCET-12-1004]
- Chinese Changjiang Scholars and Innovative Research Team in University [IRT1053]
Silent information regulator 1 (SIRT1), a type of histone deacetylase, is a highly effective therapeutic target for protection against ischemia reperfusion (IR) injury (IRI). Previous studies showed that melatonin preserves SIRT1 expression in neuronal cells of newborn rats after hypoxia-ischemia. However, the definite role of SIRT1 in the protective effect of melatonin against cerebral IRI in adult has not been explored. In this study, the brain of adult mice was subjected to IRI. Prior to this procedure, the mice were given intraperitoneal with or without the SIRT1 inhibitor, EX527. Melatonin conferred a cerebral-protective effect, as shown by reduced infarct volume, lowered brain edema, and increased neurological scores. The melatonin-induced upregulation of SIRT1 was also associated with an increase in the anti-apoptotic factor, Bcl2, and a reduction in the pro-apoptotic factor Bax. Moreover, melatonin resulted in a well-preserved mitochondrial membrane potential, mitochondrial Complex I activity, and mitochondrial cytochrome c level while it reduced cytosolic cytochrome c level. However, the melatonin-elevated mitochondrial function was reversed by EX527 treatment. In summary, our results demonstrate that melatonin treatment attenuates cerebral IRI by reducing IR-induced mitochondrial dysfunction through the activation of SIRT1 signaling.
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