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Activation of adenosine triphosphate‐sensitive potassium channels confers protection against rotenone‐induced cell death: Therapeutic implications for Parkinson's disease
Author(s) -
Tai KwokKeung,
Truong Daniel D.
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10309
Subject(s) - rotenone , pharmacology , potassium channel , xanthine oxidase , programmed cell death , parkinson's disease , adenosine triphosphate , neurotoxicity , chemistry , mitochondrion , medicine , microbiology and biotechnology , biology , biochemistry , disease , toxicity , enzyme , apoptosis
It is anticipated that further understanding of the protective mechanism induced by ischemic preconditioning will improve prognosis for patients of ischemic injury. It is not known whether preconditioning exerts beneficial actions in neurodegenerative diseases, in which ischemic injury plays a causative role. Here we show that transient activation of ATP‐sensitive potassium channels, a trigger in ischemic preconditioning signaling, confers protection in PC12 cells and SH‐SY5Y cells against neurotoxic effect of rotenone and MPTP, mitochondrial complex I inhibitors that have been implicated in the pathogenesis of Parkinson's disease. The degree of protection is in proportion to the bouts of exposure to an ATP‐sensitive potassium channel opener, a feature reminiscent of ischemic tolerance in vivo. Protection is sensitive to a protein synthesis inhibitor, indicating the involvement of de novo protein synthesis in the protective processes. Pretreatment of PC12 cells with preconditioning stimuli FeSO 4 or xanthine/xanthine oxidase also confers protection against rotenone‐induced cell death. Our results demonstrate for the first time the protective role of ATP‐sensitive potassium channels in a dopaminergic neuronal cell line against rotenone‐induced neurotoxicity and conceptually support the view that ischemic preconditioning‐derived therapeutic strategies may have potential and feasibility in therapy for Parkinson's disease. © 2002 Wiley‐Liss, Inc.