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Homer1a attenuates glutamate-induced oxidative injury in HT-22 cells through regulation of store-operated calcium entry

Calcium disequilibrium is extensively involved in oxidative stress-induced neuronal injury. Although Homer1a is known to regulate several neuronal calcium pathways, its effects on, or its exact relationship with, oxidative stress-induced neuronal injury has not yet been fully elucidated. We found th...

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Autores principales: Rao, Wei, Peng, Cheng, Zhang, Lei, Su, Ning, Wang, Kai, Hui, Hao, Dai, Shu-hui, Yang, Yue-fan, Luo, Peng, Fei, Zhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041114/
https://www.ncbi.nlm.nih.gov/pubmed/27681296
http://dx.doi.org/10.1038/srep33975
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author Rao, Wei
Peng, Cheng
Zhang, Lei
Su, Ning
Wang, Kai
Hui, Hao
Dai, Shu-hui
Yang, Yue-fan
Luo, Peng
Fei, Zhou
author_facet Rao, Wei
Peng, Cheng
Zhang, Lei
Su, Ning
Wang, Kai
Hui, Hao
Dai, Shu-hui
Yang, Yue-fan
Luo, Peng
Fei, Zhou
author_sort Rao, Wei
collection PubMed
description Calcium disequilibrium is extensively involved in oxidative stress-induced neuronal injury. Although Homer1a is known to regulate several neuronal calcium pathways, its effects on, or its exact relationship with, oxidative stress-induced neuronal injury has not yet been fully elucidated. We found that Homer1a protected HT-22 cells from glutamate-induced oxidative stress injury by inhibiting final-phase intracellular calcium overload and mitochondrial oxidative stress. In these cells, stromal interactive molecule 1 (STIM1) puncta, but not the protein level, was significantly increased after glutamate treatment. Store-operated calcium entry (SOCE) inhibitors and cells in which a key component of SOCE (STIM1) was knocked out were used as glutamate-induced oxidative stress injury models. Both models demonstrated significant improvement of HT-22 cell survival after glutamate treatment. Additionally, increased Homer1a protein levels significantly inhibited SOCE and decreased the association of STIM1-Orai1 triggered by glutamate. These results suggest that up-regulation of Homer1a can protect HT-22 cells from glutamate-induced oxidative injury by disrupting the STIM1-Oria1 association, and then by inhibiting the SOCE-mediated final-phrase calcium overload. Thus, regulation of Homer1a, either alone or in conjunction with SOCE inhibition, may serve as key therapeutic interventional targets for neurological diseases in which oxidative stress is involved in the etiology or progression of the disease.
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spelling pubmed-50411142016-09-30 Homer1a attenuates glutamate-induced oxidative injury in HT-22 cells through regulation of store-operated calcium entry Rao, Wei Peng, Cheng Zhang, Lei Su, Ning Wang, Kai Hui, Hao Dai, Shu-hui Yang, Yue-fan Luo, Peng Fei, Zhou Sci Rep Article Calcium disequilibrium is extensively involved in oxidative stress-induced neuronal injury. Although Homer1a is known to regulate several neuronal calcium pathways, its effects on, or its exact relationship with, oxidative stress-induced neuronal injury has not yet been fully elucidated. We found that Homer1a protected HT-22 cells from glutamate-induced oxidative stress injury by inhibiting final-phase intracellular calcium overload and mitochondrial oxidative stress. In these cells, stromal interactive molecule 1 (STIM1) puncta, but not the protein level, was significantly increased after glutamate treatment. Store-operated calcium entry (SOCE) inhibitors and cells in which a key component of SOCE (STIM1) was knocked out were used as glutamate-induced oxidative stress injury models. Both models demonstrated significant improvement of HT-22 cell survival after glutamate treatment. Additionally, increased Homer1a protein levels significantly inhibited SOCE and decreased the association of STIM1-Orai1 triggered by glutamate. These results suggest that up-regulation of Homer1a can protect HT-22 cells from glutamate-induced oxidative injury by disrupting the STIM1-Oria1 association, and then by inhibiting the SOCE-mediated final-phrase calcium overload. Thus, regulation of Homer1a, either alone or in conjunction with SOCE inhibition, may serve as key therapeutic interventional targets for neurological diseases in which oxidative stress is involved in the etiology or progression of the disease. Nature Publishing Group 2016-09-29 /pmc/articles/PMC5041114/ /pubmed/27681296 http://dx.doi.org/10.1038/srep33975 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Rao, Wei
Peng, Cheng
Zhang, Lei
Su, Ning
Wang, Kai
Hui, Hao
Dai, Shu-hui
Yang, Yue-fan
Luo, Peng
Fei, Zhou
Homer1a attenuates glutamate-induced oxidative injury in HT-22 cells through regulation of store-operated calcium entry
title Homer1a attenuates glutamate-induced oxidative injury in HT-22 cells through regulation of store-operated calcium entry
title_full Homer1a attenuates glutamate-induced oxidative injury in HT-22 cells through regulation of store-operated calcium entry
title_fullStr Homer1a attenuates glutamate-induced oxidative injury in HT-22 cells through regulation of store-operated calcium entry
title_full_unstemmed Homer1a attenuates glutamate-induced oxidative injury in HT-22 cells through regulation of store-operated calcium entry
title_short Homer1a attenuates glutamate-induced oxidative injury in HT-22 cells through regulation of store-operated calcium entry
title_sort homer1a attenuates glutamate-induced oxidative injury in ht-22 cells through regulation of store-operated calcium entry
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041114/
https://www.ncbi.nlm.nih.gov/pubmed/27681296
http://dx.doi.org/10.1038/srep33975
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