Estradiol prevents the injury-induced decrease of Akt/glycogen synthase kinase 3beta phosphorylation.
Estradiol prevents neuronal cell death through the activation of cell survival signals and the inhibition of apoptotic signals. This study investigated whether estradiol modulates the anti-apoptotic signal through the phosphorylation of Akt and its downstream target, glycogen synthase kinase 3beta (GSK3beta). Adult female rats were ovariectomized 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 Ser(473) and GSK3beta at Ser(9) using Western blot analysis and immunohistochemistry. Estradiol prevented the injury-induced decrease of pAkt and pGSK3beta. Furthermore, pretreatment with estradiol decreased glutamate toxicity-induced cell death in a hippocampal cell line (HT22). Also, estradiol prevented the glutamate toxicity-induced decrease of pAkt and pGSK3beta in HT22 cells. Our findings suggest that estradiol plays a potent protective role against brain injury and that phosphorylation of Akt and GSK3beta by estradiol mediated these protective effects.
Koh
Phil Ok
PO
Department of Anatomy, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, 900 Gajwa-dong, Jinju, South Korea. pokoh@gsnu.ac.kr
Won
Chung Kil
CK
Cho
Jae Hyun
JH
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D020520:Brain Infarction / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D002460:Cell Line; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000633:toxicity; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D018698:Glutamic Acid; D004958:Estradiol; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3