Koh Phil-Ok
Department of Anatomy, College of Veterinary Medicine and Institute of Agriculture and Life Science, Gyeongsang National University, South Korea.
J Vet Med Sci. 2007 Mar;69(3):285-8. doi: 10.1292/jvms.69.285.
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 17beta-estradiol decreased glutamate toxicity-induced cell death in HT22 cells. Also, pretreatment with 17beta-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. 17Beta-estradiol pretreatment prevented the glutamate-induced decrease of pAkt, pBad, pFKHR, and pFKHRL1. These findings clearly confirm that 17beta-estradiol plays a potent neuroprotective role against glutamate-induced toxicity and suggest that phosphorylation of Akt and its downstream targets by 17beta-estradiol mediated these protective effects.
