Melatonin prevents cell death and mitochondrial dysfunction via a SIRT1-dependent mechanism during ischemic-stroke in mice

Yang Yang, Shuai Jiang, Yushu Dong, Chongxi Fan, Lei Zhao, Xiangmin Yang, Juan Li, Shouyin Di, Liang Yue, Guobiao Liang, Russel J. Reiter, Yan Qu

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)61-70
Number of pages10
JournalJournal of pineal research
Volume58
Issue number1
DOIs
StatePublished - Jan 2015

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Keywords

  • SIRT1 signaling
  • cerebral-protection
  • ischemia reperfusion
  • melatonin
  • mitochondrial dysfunction

ASJC Scopus subject areas

  • Endocrinology

Cite this

Yang, Y., Jiang, S., Dong, Y., Fan, C., Zhao, L., Yang, X., Li, J., Di, S., Yue, L., Liang, G., Reiter, R. J., & Qu, Y. (2015). Melatonin prevents cell death and mitochondrial dysfunction via a SIRT1-dependent mechanism during ischemic-stroke in mice. Journal of pineal research, 58(1), 61-70. https://doi.org/10.1111/jpi.12193