Publication Date:
2015-01-23
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 is implicated in the pathogenesis of neurodegeneration. Thus, it is important to identify neuronal pathways/factors controlling apoptosis. Pink1 (PTEN-induced kinase 1)is a ubiquitously expressed gene and have been reproted 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. Here, we demonstrate that thapsigargin, a specific irreversible inhibitor of ER calcium-ATPase,could lead to dramatic oxidative stress and neuronal apoptosis by ectopic calcium entry. Importantly, the neuronal toxicity of thapsigargin inhibits anti-oxidant gene Pink1 expression. While Pink1 knockdown enhanced the neuronal apoptosis by thapsigargin and 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.
Print ISSN:
0144-8463
Electronic ISSN:
1573-4935
Topics:
Biology
,
Chemistry and Pharmacology
Permalink