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 were subjected to IRI. Prior to this procedure, the mice were given intraperitoneal with or without the SIRT1 inhibitor, EX527. Melatonin conferred a cerebralprotective effect, as shown by reduced infarct volume, lowered brain edema and increased neurological scores. The melatonin-induced up-regulation 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 (MMP), mitochondria Complex I activity, mitochondrial cytochrome c level while it reduced cytosolic cytochrome c level. However, the This article is protected by copyright. All rights reserved.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.
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
Department of Neurosurgery,Xijing Hospital,The Fourth Military Medical University,127 Changle West R Department of Neurosurgery,Xijing Hospital,The Fourth Military Medical University,127 Changle West R Department of Neurosurgery,General Hospital of Shenyang Military Area Command,83 Wenhua Road,Shenyan Department of Thoracic Surgery,Tangdu Hospital,The Fourth Military Medical University,1 Xinsi Road,X Department of Cellular and Structural Biology,UT Health Science Center,7703 Floyd Curl Drive,San Ant