Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6271574 | Neuroscience | 2015 | 18 Pages |
Abstract
It is well known that estrogen exerts neuroprotective effect against various neuronal damages. However, the estrogen receptor (ER) that mediates estrogen neuroprotection has not been well established. In this study, we investigated the potential receptor that mediates estrogen neuroprotection and the underlying molecular mechanisms. Hydrogen peroxide (H2O2) was chosen as an agent in our study to mimic free radicals that are often involved in the pathogenesis of many degenerative diseases. We found that in human SY5Y and IMR-32 cells, the estrogen neuroprotection against H2O2 toxicity was abrogated by knockdown of a variant of estrogen receptor-α, ER-α36. We also studied the rapid estrogen signaling mediated by ER-α36 in neuroprotective effect and found the PI3K/AKT and MAPK/ERK1/2 signaling mediated by ER-α36 is involved in estrogen neuroprotection. We also found that GPER, an orphan G protein-coupled receptor, is not involved in ER-α36-mediated rapid estrogen response. Our study thus demonstrates that ER-α36-mediated rapid estrogen signaling is involved in the neuroprotection activity of estrogen against oxidative toxicity.
Keywords
Rapid estrogen signalingER-α36FBSGPERFITCPVDFECLBCA17β-estradiol3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromideDMEM/F12DMSOG protein–coupled receptorMTTSmall interfering RNAsiRNAHydrogen peroxideenhanced chemiluminescencebicinchoninic acidAlzheimer’s diseaseDimethyl sulfoxidefetal bovine serumOxidative toxicityfluorescein isothiocyanateNeuroprotectionH2O2Propidium iodidePolyvinylidene fluorideEstrogen receptor
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Authors
S. Han, B. Zhao, X. Pan, Z. Song, J. Liu, Y. Gong, M. Wang,