title: Role of ERK signaling in the neuroprotective efficacy of magnesium sulfate treatment during focal cerebral ischemia in the gerbil cortex.
abstract: Magnesium sulfate (MgSO4) ameliorates focal ischemia-induced neuronal death in the rat and gerbil models. However, the molecular mechanisms for this neuroprotection are not known. Focal cerebral ischemia was produced by unilateral occlusion of the right common carotid artery and the right middle cerebral artery (CCAO + MCAO) for 30 min or 60 min. Treatment with MgSO4 significantly increased the level of mitogen-activated protein kinase/extra-cellular signal-regulated kinase kinase 1/2 (MEK1/2), extra-cellular signal-regulated kinase 1/2 (ERK1/2), cyclic-AMP response element binding protein (CREB) phosphorylation and the anti-apoptotic protein Bcl-2 both in the non-ischemic (contralateral) and ischemic (ipsilateral) cortex. However, these effects were reversed by administration of U0126, a MEK kinase inhibitor. In the ipsilateral cortex, a significant increase in the level of the proapoptotic proteins Bax, Bad, BNIP3 and activated caspase 3 were detected at the end of focal ischemia compared to the non-ischemic cortex. Treatment of MgSO4 prevented these ischemia-induced activations of the death cascade. Collectively, these data indicate that the ERK-CREB-Bcl-2 signaling pathway might be involved in MgSO4-induced neuroprotection following focal ischemia. Moreover, MgSO4 treatment also resulted in a reduction in pro-apoptotic proteins. These results enhance our understanding on the role of MgSO4 in treating cerebral ischemia.
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, Republic of China.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Liou
authors.forename: Shu-Ying
authors.initials: SY
authors.lastname: Chung
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Lin
authors.forename: Gwo-Ping
authors.initials: GP
authors.lastname: Jong
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Yi-Chang
authors.initials: YC
authors.lastname: Cheng
authors.forename: Fu-Chou
authors.initials: FC
authors.lastname: Cheng
authors.forename: Jing-Ying
authors.initials: JY
authors.lastname: Lin
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005849:Gerbillinae; D008278:Magnesium Sulfate / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D023421:Models, Animal; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D008278:Magnesium Sulfate; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3