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G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice
Spinal cord injury (SCI) always occurs accidently and leads to motor dysfunction because of biochemical and pathological events. Estrogen has been shown to be neuroprotective against SCI through estrogen receptors (ERs), but the underlying mechanisms have not been fully elucidated. In the present st...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006313/ https://www.ncbi.nlm.nih.gov/pubmed/27407175 http://dx.doi.org/10.1042/BSR20160134 |
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author | Cheng, Qiang Meng, Jia Wang, Xin-shang Kang, Wen-bo Tian, Zhen Zhang, Kun Liu, Gang Zhao, Jian-ning |
author_facet | Cheng, Qiang Meng, Jia Wang, Xin-shang Kang, Wen-bo Tian, Zhen Zhang, Kun Liu, Gang Zhao, Jian-ning |
author_sort | Cheng, Qiang |
collection | PubMed |
description | Spinal cord injury (SCI) always occurs accidently and leads to motor dysfunction because of biochemical and pathological events. Estrogen has been shown to be neuroprotective against SCI through estrogen receptors (ERs), but the underlying mechanisms have not been fully elucidated. In the present study, we investigated the role of a newly found membrane ER, G protein-coupled estrogen receptor 1 (GPR30 or GPER1), and discussed the feasibility of a GPR30 agonist as an estrogen replacement. Forty adult female C57BL/6J mice (10–12 weeks old) were divided randomly into vehicle, G-1, E2, G-1 + G-15 and E2 + G-15 groups. All mice were subjected to SCI using a crushing injury approach. The specific GPR30 agonist, G-1, mimicked the effects of E2 treatment by preventing SCI-induced apoptotic cell death and enhancing motor functional recovery after injury. GPR30 activation regulated phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK/extracellular signal-regulated kinase (ERK) signalling pathways, increased GPR30 and anti-apoptosis proteins Bcl-2 and brain derived neurotrophic factor (BDNF), but decreased the pro-apoptosis factor Bax and cleaved caspase-3. However, the neuroprotective effects of G-1 and E2 were blocked by the specific GPR30 antagonist, G-15. Thus, GPR30 rather than classic ERs is required to induce estrogenic neuroprotective effects. Given that estrogen replacement therapy may cause unexpected side effects, especially on the reproductive system, GPR30 agonists may represent a potential therapeutic approach for treating SCI. |
format | Online Article Text |
id | pubmed-5006313 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-50063132016-09-09 G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice Cheng, Qiang Meng, Jia Wang, Xin-shang Kang, Wen-bo Tian, Zhen Zhang, Kun Liu, Gang Zhao, Jian-ning Biosci Rep Original Papers Spinal cord injury (SCI) always occurs accidently and leads to motor dysfunction because of biochemical and pathological events. Estrogen has been shown to be neuroprotective against SCI through estrogen receptors (ERs), but the underlying mechanisms have not been fully elucidated. In the present study, we investigated the role of a newly found membrane ER, G protein-coupled estrogen receptor 1 (GPR30 or GPER1), and discussed the feasibility of a GPR30 agonist as an estrogen replacement. Forty adult female C57BL/6J mice (10–12 weeks old) were divided randomly into vehicle, G-1, E2, G-1 + G-15 and E2 + G-15 groups. All mice were subjected to SCI using a crushing injury approach. The specific GPR30 agonist, G-1, mimicked the effects of E2 treatment by preventing SCI-induced apoptotic cell death and enhancing motor functional recovery after injury. GPR30 activation regulated phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK/extracellular signal-regulated kinase (ERK) signalling pathways, increased GPR30 and anti-apoptosis proteins Bcl-2 and brain derived neurotrophic factor (BDNF), but decreased the pro-apoptosis factor Bax and cleaved caspase-3. However, the neuroprotective effects of G-1 and E2 were blocked by the specific GPR30 antagonist, G-15. Thus, GPR30 rather than classic ERs is required to induce estrogenic neuroprotective effects. Given that estrogen replacement therapy may cause unexpected side effects, especially on the reproductive system, GPR30 agonists may represent a potential therapeutic approach for treating SCI. Portland Press Ltd. 2016-08-31 /pmc/articles/PMC5006313/ /pubmed/27407175 http://dx.doi.org/10.1042/BSR20160134 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution Licence 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Papers Cheng, Qiang Meng, Jia Wang, Xin-shang Kang, Wen-bo Tian, Zhen Zhang, Kun Liu, Gang Zhao, Jian-ning G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice |
title | G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice |
title_full | G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice |
title_fullStr | G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice |
title_full_unstemmed | G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice |
title_short | G-1 exerts neuroprotective effects through G protein-coupled estrogen receptor 1 following spinal cord injury in mice |
title_sort | g-1 exerts neuroprotective effects through g protein-coupled estrogen receptor 1 following spinal cord injury in mice |
topic | Original Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006313/ https://www.ncbi.nlm.nih.gov/pubmed/27407175 http://dx.doi.org/10.1042/BSR20160134 |
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