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Role of PI3K/Akt in diazoxide preconditioning against rat hippocampal neuronal death in pilocarpine-induced seizures.
Brain Res. 2011 Apr 06; 1383:135-40.BR

Abstract

Diazoxide (DZ), a highly selective opener of the mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel, has neuroprotective effects. However, the mechanism of DZ protecting hippocampal neurons against cell death in pilocarpine-induced seizures is unknown. In this study, we investigated DZ attenuating neuronal loss caused by pilocarpine-induced seizures in rat hippocampus. DZ inhibited seizure-induced change in phospho-Akt expression, translocation of apoptosis-inducing factor (AIF), release of cytochrome c (CytC) and caspase-3 activation, which could be abolished by preincubation with 5-hydroxydecanoic acid, an inhibitor of mitoK(ATP). In addition, wortmannin, an inhibitor of phosphatidylinositol-3-kinase (PI3K), attenuated the translocation of AIF, CytC release and caspase-3 activation after seizures. DZ could reduce neuronal death induced by seizures in hippocampus by suppressing the translocation of AIF, CytC release and the activation of caspase-3 via the PI3K/Akt pathway.

Authors+Show Affiliations

Department of Neurology, Qilu Hospital, Shandong University, 44#, Wenhua Xi Road, Jinan 250012, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21256120

Citation

Xue, Yuan, et al. "Role of PI3K/Akt in Diazoxide Preconditioning Against Rat Hippocampal Neuronal Death in Pilocarpine-induced Seizures." Brain Research, vol. 1383, 2011, pp. 135-40.
Xue Y, Xie N, Lin Y, et al. Role of PI3K/Akt in diazoxide preconditioning against rat hippocampal neuronal death in pilocarpine-induced seizures. Brain Res. 2011;1383:135-40.
Xue, Y., Xie, N., Lin, Y., Xu, J., Han, Y., Wang, S., Jiang, H., & Chi, Z. (2011). Role of PI3K/Akt in diazoxide preconditioning against rat hippocampal neuronal death in pilocarpine-induced seizures. Brain Research, 1383, 135-40. https://doi.org/10.1016/j.brainres.2011.01.037
Xue Y, et al. Role of PI3K/Akt in Diazoxide Preconditioning Against Rat Hippocampal Neuronal Death in Pilocarpine-induced Seizures. Brain Res. 2011 Apr 6;1383:135-40. PubMed PMID: 21256120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of PI3K/Akt in diazoxide preconditioning against rat hippocampal neuronal death in pilocarpine-induced seizures. AU - Xue,Yuan, AU - Xie,Nanchang, AU - Lin,Youting, AU - Xu,Jingjing, AU - Han,Yuxiang, AU - Wang,Shengjun, AU - Jiang,Hong, AU - Chi,Zhaofu, Y1 - 2011/01/20/ PY - 2010/11/11/received PY - 2011/01/11/revised PY - 2011/01/12/accepted PY - 2011/1/25/entrez PY - 2011/1/25/pubmed PY - 2011/8/4/medline SP - 135 EP - 40 JF - Brain research JO - Brain Res VL - 1383 N2 - Diazoxide (DZ), a highly selective opener of the mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel, has neuroprotective effects. However, the mechanism of DZ protecting hippocampal neurons against cell death in pilocarpine-induced seizures is unknown. In this study, we investigated DZ attenuating neuronal loss caused by pilocarpine-induced seizures in rat hippocampus. DZ inhibited seizure-induced change in phospho-Akt expression, translocation of apoptosis-inducing factor (AIF), release of cytochrome c (CytC) and caspase-3 activation, which could be abolished by preincubation with 5-hydroxydecanoic acid, an inhibitor of mitoK(ATP). In addition, wortmannin, an inhibitor of phosphatidylinositol-3-kinase (PI3K), attenuated the translocation of AIF, CytC release and caspase-3 activation after seizures. DZ could reduce neuronal death induced by seizures in hippocampus by suppressing the translocation of AIF, CytC release and the activation of caspase-3 via the PI3K/Akt pathway. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/21256120/Role_of_PI3K/Akt_in_diazoxide_preconditioning_against_rat_hippocampal_neuronal_death_in_pilocarpine_induced_seizures_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(11)00098-9 DB - PRIME DP - Unbound Medicine ER -