Estradiol attenuates the focal cerebral ischemic injury through mTOR/p70S6 kinase signaling pathway.
We previously showed that estradiol prevents neuronal cell death through the activation of Akt and its downstream targets Bad and FKHR. This study investigated whether estradiol modulates the survival pathway through other downstream targets of Akt, including mammalian target of rapamycin (mTOR) and p70S6 kinase. It is known that mTOR is a downstream target of Akt and a central regulator of protein synthesis, cell growth, and cell cycle progression. Adult female rats were ovariectomied and treated with estradiol prior to middle cerebral artery occlusion (MCAO). Brains were collected 24h after MCAO and infarct volumes were analyzed. We confirmed that estradiol significantly reduces infarct volume and decreases the number of positive cells for TUNEL staining in the cerebral cortex. Brain injury-induced a decrease in phospho-mTOR and phospho-p70S6 kinase. Estradiol prevented the injury-induced decrease in Akt activation and phosphorylation of mTOR and p70S6 kinases, and the subsequent decrease in S6 phosphorylation. Our findings suggest that estradiol plays a potent protective role against brain injury by preventing the injury-induced decrease of mTOR and p70S6 kinase phosphorylation.
Koh
Phil-Ok
PO
Department of Anatomy, College of Veterinary Medicine, Institute of Agriculture and Life Science, Gyeongsang National University, 900 Gajwa-dong, Jinju 660-701, South Korea. pokoh@gsnu.ac.kr
Cho
Jae-Hyeon
JH
Won
Chung-Kil
CK
Lee
Hyo-Jong
HJ
Sung
Jin-Hee
JH
Kim
Myeong-Ok
MO
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D010766:Phosphorylation; D011494:Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
D004967:Estrogens; D004958:Estradiol; D011494:Protein Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases