akt-i-1-2-compound and Cerebral-Infarction
akt-i-1-2-compound has been researched along with Cerebral-Infarction* in 1 studies
Other Studies
1 other study(ies) available for akt-i-1-2-compound and Cerebral-Infarction
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Neuroprotective effect of humanin on cerebral ischemia/reperfusion injury is mediated by a PI3K/Akt pathway.
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. Topics: Androstadienes; Animals; Benzylamines; Blotting, Western; Brain; Brain Ischemia; Cell Death; Cell Hypoxia; Cell Survival; Cells, Cultured; Cerebral Infarction; Glucose; Infarction, Middle Cerebral Artery; Injections, Intraventricular; Intracellular Signaling Peptides and Proteins; Male; Mice; Neurons; Neuroprotective Agents; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Quinoxalines; Reperfusion Injury; Signal Transduction; Wortmannin | 2008 |