title: Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis.
abstract: 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.
authors.affiliation: *Department of Bioengineering, College of Materials and Chemistry Chemical Engineering, Chengdu University of Technology, Chengdu, 610059, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: *Department of Bioengineering, College of Materials and Chemistry Chemical Engineering, Chengdu University of Technology, Chengdu, 610059, China.
authors.forename: Guo-ku
authors.initials: GK
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D055785:Gene Knockdown Techniques; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D019284:Thapsigargin / Q000009:adverse effects*; D015854:Up-Regulation; D000099202:PTEN-Induced Putative Kinase
chemical_list: D002118:Calcium; D004791:Enzyme Inhibitors; D011494:Protein Kinases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019284:Thapsigargin; D000099202:PTEN-Induced Putative Kinase