Interactions between SIRT1 and MAPK/ERK regulate neuronal apoptosis induced by traumatic brain injury in vitro and in vivo

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• 作者：Yongbo Zhao ; Peng Luo ; Qindong Guo ; Sanzhong Li ; Lei Zhang ; Mingming Zhao ; Haoxiang Xu ; Yuefan Yang ; Waisang Poon ; Zhou Fei
• 关键词：SIRT1 ; ERK ; Salermide ; Traumatic brain injury ; Apoptosis
• 刊名：Experimental Neurology
• 出版年：2012
• 出版时间：October, 2012
• 年：2012
• 卷：237
• 期：2
• 页码：489-498
• 全文大小：1056 K

文摘

Traumatic brain injury (TBI) is a serious insult that frequently leads to neurological dysfunction or death. Silent information regulator family protein 1 (SIRT1), as the founding member of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, has recently been demonstrated to have neuroprotective effect in several models of neurodegenerative diseases. The present study attempts to determine whether SIRT1 has a neuroprotective effect in the model of TBI, and further to investigate the possible regulatory mechanism of neuron death. Thus, we employ transection model in vitro and weight-drop model in vivo to mimic the insults of TBI. The study shows that the expressions of SIRT1, phosphorylation extracellular signal-regulated kinase (p-ERK) and cleaved Caspase-3 are induced after trauma injury in vitro or in vivo. Furthermore, inhibiting SIRT1 by pharmacological inhibitor salermide or SIRT1 siRNA significantly promotes apoptotic neuron death and reduces ERK1/2 activation induced by mechanical injury in vitro and in vivo. Inhibition of ERK1/2 activation with PD98059 or U0126 (two mitogen activated protein kinase kinase inhibitors) in vitro and in vivo significantly attenuates the SIRT1 and cleaved Caspase-3 expression to protect neuron against TBI-induced apoptosis. These results reveal that SIRT1 plays a neuroprotective effect against neuronal apoptosis induced by TBI. The interactions between SIRT1 and MAPK/ERK pathway regulate neuronal apoptosis induced by mechanical trauma injury in vitro and in vivo.