17Beta-estradiol prevents the glutamate-induced decrease of Akt and its downstream targets in HT22 cells.
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.
Koh
Phil-Ok
PO
Department of Anatomy, College of Veterinary Medicine and Institute of Agriculture and Life Science, Gyeongsang National University, South Korea.
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology*; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D051379:Mice; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000378:metabolism
C494820:Bad protein, mouse; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; C467200:Foxo1 protein, mouse; D051025:bcl-Associated Death Protein; D018698:Glutamic Acid; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt