کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4326025 | 1614056 | 2011 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Role of PI3K/Akt in diazoxide preconditioning against rat hippocampal neuronal death in pilocarpine-induced seizures Role of PI3K/Akt in diazoxide preconditioning against rat hippocampal neuronal death in pilocarpine-induced seizures](/preview/png/4326025.png)
Diazoxide (DZ), a highly selective opener of the mitochondrial ATP-sensitive potassium (mitoKATP) 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 mitoKATP. 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.
Research Highlights
► Diazoxide (DZ) attenuates the neuronal loss in pilocarpine-induced seizures.
► DZ inhibits the changes of phospho-Akt, AIF, CytC and caspase-3 after seizures.
► The changes that DZ-induced can be abolished by preconditioning with wortmannin (WTN).
► DZ protects neuron by suppressing the levels of above proteins via PI3K/Akt pathway.
Journal: Brain Research - Volume 1383, 6 April 2011, Pages 135–140