In:
Journal of Pineal Research, Wiley, Vol. 58, No. 1 ( 2015-01), p. 61-70
Abstract:
Silent information regulator 1 ( SIRT 1), 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 SIRT 1 expression in neuronal cells of newborn rats after hypoxia–ischemia. However, the definite role of SIRT 1 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 SIRT 1 inhibitor, EX 527. Melatonin conferred a cerebral‐protective effect, as shown by reduced infarct volume, lowered brain edema, and increased neurological scores. The melatonin‐induced upregulation of SIRT 1 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 EX 527 treatment. In summary, our results demonstrate that melatonin treatment attenuates cerebral IRI by reducing IR ‐induced mitochondrial dysfunction through the activation of SIRT 1 signaling.
Type of Medium:
Online Resource
ISSN:
0742-3098
,
1600-079X
DOI:
10.1111/jpi.2014.58.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2027992-9
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