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 language | English (US) |
|---|---|
| Pages (from-to) | 61-70 |
| Number of pages | 10 |
| Journal | Journal of Pineal Research |
| Volume | 58 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2015 |
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Keywords
- cerebral-protection
- ischemia reperfusion
- melatonin
- mitochondrial dysfunction
- SIRT1 signaling
ASJC Scopus subject areas
- Endocrinology
Cite this
Melatonin prevents cell death and mitochondrial dysfunction via a SIRT1-dependent mechanism during ischemic-stroke in mice. / Yang, Yang; Jiang, Shuai; Dong, Yushu; Fan, Chongxi; Zhao, Lei; Yang, Xiangmin; Li, Juan; Di, Shouyin; Yue, Liang; Liang, Guobiao; Reiter, Russel J; Qu, Yan.
In: Journal of Pineal Research, Vol. 58, No. 1, 2015, p. 61-70.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Melatonin prevents cell death and mitochondrial dysfunction via a SIRT1-dependent mechanism during ischemic-stroke in mice
AU - Yang, Yang
AU - Jiang, Shuai
AU - Dong, Yushu
AU - Fan, Chongxi
AU - Zhao, Lei
AU - Yang, Xiangmin
AU - Li, Juan
AU - Di, Shouyin
AU - Yue, Liang
AU - Liang, Guobiao
AU - Reiter, Russel J
AU - Qu, Yan
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - cerebral-protection
KW - ischemia reperfusion
KW - melatonin
KW - mitochondrial dysfunction
KW - SIRT1 signaling
UR - http://www.scopus.com/inward/record.url?scp=84919621569&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84919621569&partnerID=8YFLogxK
U2 - 10.1111/jpi.12193
DO - 10.1111/jpi.12193
M3 - Article
VL - 58
SP - 61
EP - 70
JO - Journal of Pineal Research
JF - Journal of Pineal Research
SN - 0742-3098
IS - 1
ER -