Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis

被引:40
|
作者
Li, Lin [1 ]
Hu, Guo-ku [1 ]
机构
[1] Chengdu Univ Technol, Coll Mat & Chem Chem Engn, Dept Bioengn, Chengdu 610059, Peoples R China
基金
中国国家自然科学基金;
关键词
apoptosis; phosphatase and tensin homologue (PTEN)-induced kinase 1; neurons; oxidative stress; CELL-DEATH; SUPEROXIDE-DISMUTASE; DISEASE; CA2+; MITOCHONDRIA; MECHANISMS; CALCIUM; PARKIN;
D O I
10.1042/BSR20140104
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
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页数:8
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