Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Lin, Hu, Guo-ku
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2015
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
_version_ 1782359004253519872
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
work_keys_str_mv AT lilin pink1protectscorticalneuronsfromthapsigargininducedoxidativestressandneuronalapoptosis
AT huguoku pink1protectscorticalneuronsfromthapsigargininducedoxidativestressandneuronalapoptosis