Brain Res 2010,
PMID: 20114038
Jover-Mengual, Teresa; Miyawaki, Takahiro; Latuszek, Adrianna; Alborch, Enrique; Zukin, R Suzanne; Etgen, Anne M
Global ischemia arising during cardiac arrest or cardiac surgery causes highly selective, delayed death of hippocampal CA1 neurons. Exogenous estradiol ameliorates global ischemia-induced neuronal death and cognitive impairment in male and female rodents. However, the molecular mechanisms by which a single acute injection of estradiol administered after the ischemic event intervenes in global ischemia-induced apoptotic cell death are unclear. Here we show that acute estradiol acts via the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling cascade to protect CA1 neurons in ovariectomized female rats. We demonstrate that global ischemia promotes early activation of glycogen synthase kinase-3beta (GSK3beta) and forkhead transcription factor of the O class (FOXO)3A, known Akt targets that are related to cell survival, and activation of caspase-3. Estradiol prevents ischemia-induced dephosphorylation and activation of GSK3beta and FOXO3A, and the caspase death cascade. These findings support a model whereby estradiol acts by activation of PI3K/Akt signaling to promote neuronal survival in the face of global ischemia.
Diseases/Pathways annotated by Medline MESH: Brain Ischemia, Nerve Degeneration
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Text Mining Data
transcription factor → caspase-3: "
We demonstrate that global ischemia promotes early
activation of glycogen synthase kinase-3beta ( GSK3beta ) and forkhead
transcription factor of the O class ( FOXO)3A, known Akt targets that are related to cell survival, and activation of
caspase-3
"
caspase-3 → glycogen synthase kinase-3beta: "
We demonstrate that global ischemia promotes early activation of glycogen synthase kinase-3beta ( GSK3beta ) and forkhead transcription factor of the O class ( FOXO)3A, known Akt targets that are related to cell survival, and activation of caspase-3
"
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