Estradiol prevents the focal cerebral ischemic injury-induced decrease of forkhead transcription factors phosphorylation.
Estradiol prevents neuronal cell death through the inhibition of apoptotic signals. This study investigated whether estradiol modulates the anti-apoptotic signal through the activation of Akt and its downstream targets, including forkhead transcription factors FKHR and FHKRL1. Adult female rats were ovariectomied and treated with estradiol prior to middle cerebral artery occlusion (MCAO). Brains were collected 24 h after MCAO and infarct volumes were analyzed. Estradiol administration significantly reduced infarct volume and decreased the positive cells of TUNEL staining in the cerebral cortex. Potential activation was measured by phosphorylation of Akt at Ser473, pFKHR at Ser256, and pFKHRL1 at Thr32 using Western blot analysis and immunohistochemistry. Estradiol prevents the injury-induced decrease of pAkt, pFKHR, and pFKHRL1. Further, in the presence of estradiol, the interaction of pFKHRL1 and 14-3-3 increased, compared to that of oil-treated animals. Our findings suggest that estradiol plays a potent protective role against brain injury and that Akt activation and FKHR phosphorylation by estradiol mediated these protective effects.
Won
Chung Kil
CK
Department of Anatomy, College of Veterinary Medicine and Institute of Animal Medicine, Gyeongsang National University, 900 Gajwa-dong, Jinju 660-701, South Korea.
Ji
Hyun Hwa
HH
Koh
Phil Ok
PO
D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010052:Ovariectomy; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071161:Forkhead Box Protein O1
D048948:14-3-3 Proteins; D004958:Estradiol; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D051057:Proto-Oncogene Proteins c-akt; C499515:FOXO3 protein, rat; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1