抄録
Estradiol is known to exert neuroprotective effect against glutamate toxicity in hippocampal-derived cell line (HT22). This study investigated whether estradiol modulates the anti-apoptotic signal through the phosphorylation of Akt and its downstream targets, including Bad, forkhead transcription factors FKHR and FKHRL1. Pretreatment with 17β-estradiol decreased glutamate toxicity-induced cell death in HT22 cells. Also, pretreatment with 17β-estradiol significantly decreased the positive cells of TUNEL stain, compared to that of only glutamate-treated cells. Potential activation was measured by phosphorylation of Akt at Ser473, Bad at Ser136, FKHR at Ser256, and FKHRL1 at Thr32 using Western blot analysis. 17β-estradiol pretreatment prevented the glutamate-induced decrease of pAkt, pBad, pFKHR, and pFKHRL1. These findings clearly confirm that 17β-estradiol plays a potent neuroprotective role against glutamate-induced toxicity and suggest that phosphorylation of Akt and its downstream targets by 17β-estradiol mediated these protective effects.
