Study of baicalein neuroprotection via enhancement of Akt and hypoxia-inducible factor-1α activities in cortical neurons

• Main Authors: Hung-Cheng Lin, 林紘正
• Other Authors: 李怡萱
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/28141472771372415911

碩士 === 臺北醫學大學 === 醫學研究所 === 95 === Glutamate-induced excitotoxicity is believed be involved in several neurodegenerative diseases, including stroke, brain/head injury, Alzheimer''s disease and Parkinson''s disease. Our previous study has demonstrated that baicalein, one of the flavonoids extracted from Scutellaria baicalensis Georgi, protects primary cortical neurons from glutamate/NMDA induced cell death. In this study, we further revealed that baicalein treatment enhanced phosphatidylinositol 3-kinase (PI3K)-mediated Akt phosphorylation, which is known to mediate survival signal in cells under detrimental insults. Furthermore, 24 h baicalein treatment dose-dependently increased the expression of luciferase reporter gene driven by human erythropoietin gene promoter that contains hypoxia-responsive element (HRE) for the binding of hypoxia-inducible factor 1α (HIF-1α); and this increase was reversed by PI3K inhibitor LY294002. Furthermore, the nuclear HIF-1α was increased by baicalein after 30 min and 60 min treatment, but this effect was not reversed by PI3K inhibitor. Chromatin immunoprecipitation (ChIP) shows that HIF-1α binds to HRE on erythropoietin (EPO) and vascular endothelial growth factor (VEGF) enhancer. In this regard, baicalein was found increasing of the EPO and VEGF gene expression by RT-PCR analysis. Consequently, the mitochondrial dysfunction resulted from glutamate and NMDA was significantly reversed baicalein pretreatment (12 or 8 hour), and this reversion was blocked by PI3K inhibitor. In conclusion, our results suggest that baicalein may activate Akt and HIF-1α, and might in turn give rise to more HIF-1α available for transactivating neuroprotective genes, EPO and VEGF, expression.