title: Estrogen receptor variant ER-α36 is involved in estrogen neuroprotection against oxidative toxicity.
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.
authors.affiliation: Department of Genetics and Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University, Jinan 250012, Shandong, China. Electronic address: hanshuaifei1987@163.com.
authors.forename: S
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Genetics and Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University, Jinan 250012, Shandong, China. Electronic address: 472946565@qq.com.
authors.forename: B
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China. Electronic address: pxh1997@126.com.
authors.forename: X
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Genetics and Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University, Jinan 250012, Shandong, China. Electronic address: 15169193767@163.com.
authors.forename: Z
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Genetics and Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University, Jinan 250012, Shandong, China. Electronic address: lzp90715@163.com.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Genetics and Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University, Jinan 250012, Shandong, China. Electronic address: yxg8@sdu.edu.cn.
authors.forename: Y
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Genetics and Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University, Jinan 250012, Shandong, China. Electronic address: wml@sdu.edu.cn.
authors.forename: M
authors.initials: M
authors.lastname: Wang
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D053492:Elafin / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D017603:Signal Detection, Psychological; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014162:Transfection
chemical_list: D017304:Annexin A5; D053492:Elafin; D047628:Estrogen Receptor alpha; D004967:Estrogens; C109584:GPER1 protein, human; D018696:Neuroprotective Agents; D016877:Oxidants; C506806:PI3 protein, human; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C000601334:estrogen receptor alpha 36, human; D004958:Estradiol; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt
keywords: ER-α36; neuroprotection; oxidative toxicity; rapid estrogen signaling