Estradiol attenuates down-regulation of PEA-15 and its two phosphorylated forms in ischemic brain injury

Abstract

Estradiol exerts a neuroprotective effect against focal cerebral ischemic injury through the inhibition ofapoptotic signals. Phosphoprotein enriched in astrocytes 15 (PEA-15) is mainly expressed in brain thatperform anti-apoptotic functions. This study investigated whether estradiol modulates the expression ofPEA-15 and two phosphorylated forms of PEA-15 (Ser 104 and Ser 116) in middle cerebral arteryocclusion (MCAO)-induced injury and glutamate exposure-induced neuronal cell death. Adult female ratswere ovariectomized to remove endogenous estradiol and treated with vehicle or estradiol prior toMCAO. Focal cerebral ischemia was induced by MCAO and cerebral cortices were collected 24 h afterMCAO. Western blot analysis indicated that estradiol prevents the MCAO-induced decrease in PEA-15,phospho-PEA-15 (Ser 104), phospho-PEA-15 (Ser 116). Glutamate exposure induced a reduction in PEA-15,phospho-PEA-15 (Ser 104), phospho-PEA-15 (Ser 116) in cultured neurons, whereas estradioltreatment attenuated the glutamate toxicity-induced decrease in the expression of these proteins. It hasbeen known that phosphorylation of PEA-15 is an important step in carrying out its anti-apoptoticfunction. Thus, these findings suggest that the regulation of PEA-15 phosphorylation by estradiolcontributes to the neuroprotective function of estradiol in ischemic brain injury.