Neuroprotective Effect of Humanin on Cerebral Ischemia/Reperfusion Injury Is Mediated by a PI3K/Akt Pathway
Document Type
Article
Publication Date
8-28-2008
Description
Humanin (HN) is an anti-apoptotic peptide that suppresses neuronal cell death induced by Alzheimer's disease, prion protein fragments, and serum deprivation. Recently, we demonstrated that Gly14-HN (HNG), a variant of HN in which the 14th amino acid serine is replaced with glycine, can decrease apoptotic neuronal death and reduce infarct volume in a focal cerebral ischemia/reperfusion mouse model. In this study, we postulate that the mechanism of HNG's neuroprotective effect is mediated by the PI3K/Akt pathway. Oxygen-glucose deprivation (OGD) was performed in cultured mouse primary cortical neurons for 60 min. The effect of HNG and PI3K/Akt inhibitors on OGD-induced cell death was examined at 24 h after reperfusion. HNG increased cell viability after OGD in primary cortical neurons, whereas the PI3K/Akt inhibitors wortmannin and Akti-1/2 attenuated the protective effect of HNG. HNG rapidly increased Akt phosphorylation, an effect that was inhibited by wortmannin and Akti-1/2. Mouse brains were injected intraventricularly with HNG before being subjected to middle cerebral artery occlusion (MCAO). HNG treatment significantly elevated p-Akt levels after cerebral I/R injury and decreased infarct volume. The protective effect of HNG on infarct size was attenuated by wortmannin and Akti-1/2. Taken as a whole, these results suggest that PI3K/Akt activation mediates HNG's protective effect against hypoxia/ischemia reperfusion injury.
Citation Information
Xu, Xingshun; Chua, Chu Chang; Gao, Jinping; Chua, Kao Wei; Wang, Hong; Hamdy, Ronald C.; and Chua, Balvin H.L.. 2008. Neuroprotective Effect of Humanin on Cerebral Ischemia/Reperfusion Injury Is Mediated by a PI3K/Akt Pathway. Brain Research. Vol.1227 12-18. https://doi.org/10.1016/j.brainres.2008.06.018 PMID: 18590709 ISSN: 0006-8993