title: Interactions between SIRT1 and MAPK/ERK regulate neuronal apoptosis induced by traumatic brain injury in vitro and in vivo.
abstract: 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.
authors: Institute of Neurosurgery, Xijing Hospital, Fourth Military Medical University, 17 Changlexi Street, Xi'an, Shaanxi Province 710032, People's Republic of China.
authors: Yongbo
authors: Y
authors: Zhao
authors: Peng
authors: P
authors: Luo
authors: Qindong
authors: Q
authors: Guo
authors: Sanzhong
authors: S
authors: Li
authors: Lei
authors: L
authors: Zhang
authors: Mingming
authors: M
authors: Zhao
authors: Haoxiang
authors: H
authors: Xu
authors: Yuefan
authors: Y
authors: Yang
authors: Waisang
authors: W
authors: Poon
authors: Zhou
authors: Z
authors: Fei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D056564:Sirtuin 1 / Q000378:metabolism*; D014162:Transfection
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1