17 beta-estradiol prevents the glutamate-induced decrease of Akt and its downstream targets in HT22 cells

Abstract

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 17 beta-estradiol decreased glutamate toxicity-induced cell death in HT22 cells. Also, pretreatment with 17 beta-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 Ser (473), Bad at Ser(136), FKHR at Ser(256), and FKHRL1 at Thr(32) using Western blot analysis. 17 beta-estradiol pretreatment prevented the glutamate-induced decrease of pAkt, pBad, pFKHR, and pFKHRL1. These findings clearly confirm that 17 beta-estradiol plays a potent neuroprotective role against glutamate-induced toxicity and suggest that phosphorylation of Akt and its downstream targets by 17 beta-estradiol mediated these protective effects.