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Inhibition of Store-Operated Calcium Entry Attenuates MPP(+)-Induced Oxidative Stress via Preservation of Mitochondrial Function in PC12 Cells: Involvement of Homer1a

The process of store-operated calcium entry (SOCE), whereby the release of intracellular Ca(2+) from endoplasmic reticulum (ER) activates Ca(2+) influx channels in the plasma membrane, has been demonstrated to impact a diverse range of cell functions. In the present study, we investigated the potent...

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Autores principales: Li, Xia, Chen, Wei, Zhang, Lei, Liu, Wen-bo, Fei, Zhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866123/
https://www.ncbi.nlm.nih.gov/pubmed/24358303
http://dx.doi.org/10.1371/journal.pone.0083638
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author Li, Xia
Chen, Wei
Zhang, Lei
Liu, Wen-bo
Fei, Zhou
author_facet Li, Xia
Chen, Wei
Zhang, Lei
Liu, Wen-bo
Fei, Zhou
author_sort Li, Xia
collection PubMed
description The process of store-operated calcium entry (SOCE), whereby the release of intracellular Ca(2+) from endoplasmic reticulum (ER) activates Ca(2+) influx channels in the plasma membrane, has been demonstrated to impact a diverse range of cell functions. In the present study, we investigated the potential protective effect of SOCE inhibition against 1-methyl-4-phenylpyridinium (MPP(+)) injury by using pharmacological antagonists or specific small interfering RNA (siRNA) in PC12 cells. The results showed that both antagonists (15 μM MRS-1845 and 50 μM ML-9) and stromal interacting molecule-1 (STIM1) targeted siRNA (Si-STIM1) significantly increased cell viability, decreased apoptotic cell death and reduced intracellular reactive oxygen species (ROS) production and lipid peroxidation in MPP(+) injured PC12 cells. SOCE inhibition also prevented MPP(+) induced mitochondrial dysfunction and activation of mitochondrial related apoptotic factors, while had no effect on mitochondrial biogenesis. Moreover, inhibition of SOCE by antagonists and siRNA increased the expression levels of Homer1a mRNA and protein, and knockdown of Homer1a expression by specific siRNA partly reversed the protective effects induced by SOCE inhibition in PC12 cells. All these results indicated that SOCE inhibition protected PC12 cells against MPP(+) insult through upregulation of Homer1a expression, and SOCE might be an ideal target for investigating therapeutic strategy against neuronal injury in PD patients.
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spelling pubmed-38661232013-12-19 Inhibition of Store-Operated Calcium Entry Attenuates MPP(+)-Induced Oxidative Stress via Preservation of Mitochondrial Function in PC12 Cells: Involvement of Homer1a Li, Xia Chen, Wei Zhang, Lei Liu, Wen-bo Fei, Zhou PLoS One Research Article The process of store-operated calcium entry (SOCE), whereby the release of intracellular Ca(2+) from endoplasmic reticulum (ER) activates Ca(2+) influx channels in the plasma membrane, has been demonstrated to impact a diverse range of cell functions. In the present study, we investigated the potential protective effect of SOCE inhibition against 1-methyl-4-phenylpyridinium (MPP(+)) injury by using pharmacological antagonists or specific small interfering RNA (siRNA) in PC12 cells. The results showed that both antagonists (15 μM MRS-1845 and 50 μM ML-9) and stromal interacting molecule-1 (STIM1) targeted siRNA (Si-STIM1) significantly increased cell viability, decreased apoptotic cell death and reduced intracellular reactive oxygen species (ROS) production and lipid peroxidation in MPP(+) injured PC12 cells. SOCE inhibition also prevented MPP(+) induced mitochondrial dysfunction and activation of mitochondrial related apoptotic factors, while had no effect on mitochondrial biogenesis. Moreover, inhibition of SOCE by antagonists and siRNA increased the expression levels of Homer1a mRNA and protein, and knockdown of Homer1a expression by specific siRNA partly reversed the protective effects induced by SOCE inhibition in PC12 cells. All these results indicated that SOCE inhibition protected PC12 cells against MPP(+) insult through upregulation of Homer1a expression, and SOCE might be an ideal target for investigating therapeutic strategy against neuronal injury in PD patients. Public Library of Science 2013-12-17 /pmc/articles/PMC3866123/ /pubmed/24358303 http://dx.doi.org/10.1371/journal.pone.0083638 Text en © 2013 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Li, Xia
Chen, Wei
Zhang, Lei
Liu, Wen-bo
Fei, Zhou
Inhibition of Store-Operated Calcium Entry Attenuates MPP(+)-Induced Oxidative Stress via Preservation of Mitochondrial Function in PC12 Cells: Involvement of Homer1a
title Inhibition of Store-Operated Calcium Entry Attenuates MPP(+)-Induced Oxidative Stress via Preservation of Mitochondrial Function in PC12 Cells: Involvement of Homer1a
title_full Inhibition of Store-Operated Calcium Entry Attenuates MPP(+)-Induced Oxidative Stress via Preservation of Mitochondrial Function in PC12 Cells: Involvement of Homer1a
title_fullStr Inhibition of Store-Operated Calcium Entry Attenuates MPP(+)-Induced Oxidative Stress via Preservation of Mitochondrial Function in PC12 Cells: Involvement of Homer1a
title_full_unstemmed Inhibition of Store-Operated Calcium Entry Attenuates MPP(+)-Induced Oxidative Stress via Preservation of Mitochondrial Function in PC12 Cells: Involvement of Homer1a
title_short Inhibition of Store-Operated Calcium Entry Attenuates MPP(+)-Induced Oxidative Stress via Preservation of Mitochondrial Function in PC12 Cells: Involvement of Homer1a
title_sort inhibition of store-operated calcium entry attenuates mpp(+)-induced oxidative stress via preservation of mitochondrial function in pc12 cells: involvement of homer1a
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866123/
https://www.ncbi.nlm.nih.gov/pubmed/24358303
http://dx.doi.org/10.1371/journal.pone.0083638
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