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Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis
Apoptosis mediates the precise and programmed natural death of neurons and is a physiologically important process in neurogenesis during maturation of the central nervous system. However, premature apoptosis and/or an aberration in apoptosis regulation are implicated in the pathogenesis of neurodege...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340272/ https://www.ncbi.nlm.nih.gov/pubmed/25608948 http://dx.doi.org/10.1042/BSR20140104 |
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author | Li, Lin Hu, Guo-ku |
author_facet | Li, Lin Hu, Guo-ku |
author_sort | Li, Lin |
collection | PubMed |
description | Apoptosis mediates the precise and programmed natural death of neurons and is a physiologically important process in neurogenesis during maturation of the central nervous system. However, premature apoptosis and/or an aberration in apoptosis regulation are implicated in the pathogenesis of neurodegeneration. Thus, it is important to identify neuronal pathways/factors controlling apoptosis. Pink1 [phosphatase and tensin homologue (PTEN)-induced kinase 1] is a ubiquitously expressed gene and has been reported to have a physiological role in mitochondrial maintenance, suppressing mitochondrial oxidative stress, fission and autophagy. However, how Pink1 is involved in neuronal survival against oxidative stress remains not well understood. In the present paper, we demonstrate that thapsigargin, a specific irreversible inhibitor of endoplasmic reticulum (ER) calcium-ATPase, could lead to dramatic oxidative stress and neuronal apoptosis by ectopic calcium entry. Importantly, the neuronal toxicity of thapsigargin inhibits antioxidant gene Pink1 expression. Although Pink1 knockdown enhances the neuronal apoptosis by thapsigargin, its overexpression restores it. Our findings have established the neuronal protective role of Pink1 against oxidative stress and afford rationale for developing new strategy to the therapy of neurodegenerative diseases. |
format | Online Article Text |
id | pubmed-4340272 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-43402722015-03-04 Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis Li, Lin Hu, Guo-ku Biosci Rep Original Paper Apoptosis mediates the precise and programmed natural death of neurons and is a physiologically important process in neurogenesis during maturation of the central nervous system. However, premature apoptosis and/or an aberration in apoptosis regulation are implicated in the pathogenesis of neurodegeneration. Thus, it is important to identify neuronal pathways/factors controlling apoptosis. Pink1 [phosphatase and tensin homologue (PTEN)-induced kinase 1] is a ubiquitously expressed gene and has been reported to have a physiological role in mitochondrial maintenance, suppressing mitochondrial oxidative stress, fission and autophagy. However, how Pink1 is involved in neuronal survival against oxidative stress remains not well understood. In the present paper, we demonstrate that thapsigargin, a specific irreversible inhibitor of endoplasmic reticulum (ER) calcium-ATPase, could lead to dramatic oxidative stress and neuronal apoptosis by ectopic calcium entry. Importantly, the neuronal toxicity of thapsigargin inhibits antioxidant gene Pink1 expression. Although Pink1 knockdown enhances the neuronal apoptosis by thapsigargin, its overexpression restores it. Our findings have established the neuronal protective role of Pink1 against oxidative stress and afford rationale for developing new strategy to the therapy of neurodegenerative diseases. Portland Press Ltd. 2015-02-25 /pmc/articles/PMC4340272/ /pubmed/25608948 http://dx.doi.org/10.1042/BSR20140104 Text en © 2015 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC-BY) (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC-BY) (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Paper Li, Lin Hu, Guo-ku Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis |
title | Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis |
title_full | Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis |
title_fullStr | Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis |
title_full_unstemmed | Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis |
title_short | Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis |
title_sort | pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340272/ https://www.ncbi.nlm.nih.gov/pubmed/25608948 http://dx.doi.org/10.1042/BSR20140104 |
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