Abstract
Ischemic neuroprotection afforded by sevoflurane preconditioning has been previously demonstrated, yet the underlying mechanism is poorly understood and likely affects a wide range of cellular activities. Several individual microRNAs have been implicated in both the pathogenesis of cerebral ischemia and cellular survival, and are capable of affecting a range of target mRNA. Conceivably, sevoflurane preconditioning may lead to alterations in ischemia-induced microRNA expression that may subsequently exert neuroprotective effects. We first examined the microRNA expression profile following transient cerebral ischemia in rats and the impact of sevoflurane preconditioning. Microarray analysis revealed that 3 microRNAs were up-regulated (>2.0 fold) and 9 were down-regulated (< 0.5 fold) following middle cerebral artery occlusion (MCAO) compared to sham controls. In particular, miR-15b was expressed at significantly high levels after MCAO. Preconditioning with sevoflurane significantly attenuated the upregulation of miR-15b at 72h after reperfusion. Bcl-2, an anti-apoptotic gene involved in the pathogenesis of cerebral ischemia, has been identified as a direct target of miR-15b. Consistent with the observed downregulation of miR-15b in sevoflurane-preconditioned brain, postischemic Bcl-2 expression was significantly increased by sevoflurane preconditioning. We identified the 3’-UTR of Bcl-2 as the target for miR-15b. Molecular inhibition of miR-15b was capable of mimicking the neuroprotective effect of sevoflurane preconditioning, suggesting that the suppression of miR-15b due to sevoflurane contributes to its ischemic neuroprotection. Thus, sevoflurane preconditioning may exert its anti-apoptotic effects by reducing the elevated expression of miR-15b following ischemic injury, allowing its target proteins, including Bcl-2, to be translated and expressed at the protein level.
Keywords: Sevoflurane, preconditioning, cerebral ischemia, microRNA, Bcl-2.
CNS & Neurological Disorders - Drug Targets
Title:miR-15b Suppression of Bcl-2 Contributes to Cerebral Ischemic Injury and is Reversed by Sevoflurane Preconditioning
Volume: 12 Issue: 3
Author(s): Hong Shi, Bao-liang Sun, Jia Zhang, Shiduo Lu, Pengyue Zhang, Hailian Wang, Qiong Yu, R. Anne Stetler, Peter S. Vosler, Jun Chen and Yanqin Gao
Affiliation:
Keywords: Sevoflurane, preconditioning, cerebral ischemia, microRNA, Bcl-2.
Abstract: Ischemic neuroprotection afforded by sevoflurane preconditioning has been previously demonstrated, yet the underlying mechanism is poorly understood and likely affects a wide range of cellular activities. Several individual microRNAs have been implicated in both the pathogenesis of cerebral ischemia and cellular survival, and are capable of affecting a range of target mRNA. Conceivably, sevoflurane preconditioning may lead to alterations in ischemia-induced microRNA expression that may subsequently exert neuroprotective effects. We first examined the microRNA expression profile following transient cerebral ischemia in rats and the impact of sevoflurane preconditioning. Microarray analysis revealed that 3 microRNAs were up-regulated (>2.0 fold) and 9 were down-regulated (< 0.5 fold) following middle cerebral artery occlusion (MCAO) compared to sham controls. In particular, miR-15b was expressed at significantly high levels after MCAO. Preconditioning with sevoflurane significantly attenuated the upregulation of miR-15b at 72h after reperfusion. Bcl-2, an anti-apoptotic gene involved in the pathogenesis of cerebral ischemia, has been identified as a direct target of miR-15b. Consistent with the observed downregulation of miR-15b in sevoflurane-preconditioned brain, postischemic Bcl-2 expression was significantly increased by sevoflurane preconditioning. We identified the 3’-UTR of Bcl-2 as the target for miR-15b. Molecular inhibition of miR-15b was capable of mimicking the neuroprotective effect of sevoflurane preconditioning, suggesting that the suppression of miR-15b due to sevoflurane contributes to its ischemic neuroprotection. Thus, sevoflurane preconditioning may exert its anti-apoptotic effects by reducing the elevated expression of miR-15b following ischemic injury, allowing its target proteins, including Bcl-2, to be translated and expressed at the protein level.
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Cite this article as:
Shi Hong, Sun Bao-liang, Zhang Jia, Lu Shiduo, Zhang Pengyue, Wang Hailian, Yu Qiong, Stetler R. Anne, Vosler Peter S., Chen Jun and Gao Yanqin, miR-15b Suppression of Bcl-2 Contributes to Cerebral Ischemic Injury and is Reversed by Sevoflurane Preconditioning, CNS & Neurological Disorders - Drug Targets 2013; 12 (3) . https://dx.doi.org/10.2174/1871527311312030011
DOI https://dx.doi.org/10.2174/1871527311312030011 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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