Estrogen Receptor (ER)-α36 Is Involved in Estrogen- and Tamoxifen-Induced Neuroprotective Effects in Ischemic Stroke Models
Autor: | Chen Fang, Xiao-Feng Liang, Wei Zou, Hongyan Li, Jinqiu Liu, Yang Liu, Qi-Qi Zhang, Jing Liu, Liang Huang, Yejun Zhang, Xiaofei Ji, Chao Han |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
MAPK/ERK pathway
medicine.medical_specialty medicine.drug_class Estrogen receptor lcsh:Medicine Pharmacology Neuroprotection PC12 Cells Brain Ischemia Internal medicine medicine Animals Humans lcsh:Science Estrogen receptor beta Multidisciplinary business.industry lcsh:R Estrogen Receptor alpha Brain Estrogens Rats Stroke Disease Models Animal Tamoxifen Endocrinology Neuroprotective Agents Estrogen Ovariectomized rat lcsh:Q business Estrogen receptor alpha hormones hormone substitutes and hormone antagonists medicine.drug Research Article |
Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 10, p e0140660 (2015) |
ISSN: | 1932-6203 |
Popis: | The neuroprotection by estrogen (E2) and tamoxifen is well documented in experimental stroke models; however, the exact mechanism is unclear. A membrane-based estrogen receptor, ER-α36, has been identified. Postmenopausal-levels of E2 act through ER-α36 to induce osteoclast apoptosis due to a prolonged activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) signaling. We hypothesized that ER-α36 may play a role in the neuroprotective activities of estrogen and tamoxifen. Here, we studied ER-α36 expression in the brain, as well as its neuroprotective effects against oxygen and glucose deprivation (OGD) in PC12 cells. We found that ER-α36 was expressed in both rat and human brain. In addition, OGD-induced cell death was prevented by l nmol/L 17β-estradiol (E2β). E2β activates the MAPK/ERK signaling pathway in PC12 cells under basal and OGD conditions by interacting with ER-α36 and also induces ER-α36 expression. Low-dose of tamoxifen up-regulated ER-α36 expression and enhanced neuronal survival in an ovariectomized ischemic stroke model. Furthermore, low-dose of tamoxifen enhanced neuroprotective effects by modulating activates or suppress ER-α36. Our results thus demonstrated that ER-α36 is involved in neuroprotective activities mediated by both estrogen and tamoxifen. |
Databáze: | OpenAIRE |
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