Activation of adenosine triphosphate-sensitive potassium channels confers protection against rotenone-induced cell death: Therapeutic implications for Parkinson's disease

• Published in: Journal of neuroscience research Vol. 69; no. 4; pp. 559 - 566
• Main Authors: Tai, Kwok-Keung, Truong, Daniel D.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 15.08.2002
• Subjects: Adenosine Triphosphate - metabolism; Animals; ATP-sensitive potassium channels; Cell Death - drug effects; Cell Death - physiology; Dose-Response Relationship, Drug; Electron Transport Complex I; Ferrous Compounds - pharmacology; Glyburide - pharmacology; Ischemic Preconditioning; Mitochondria - drug effects; Mitochondria - metabolism; NADH, NADPH Oxidoreductases - drug effects; NADH, NADPH Oxidoreductases - metabolism; Neurons - drug effects; Neurons - metabolism; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Parkinson Disease, Secondary - chemically induced; Parkinson's disease; PC12 Cells; pheochromocytoma cells; Pinacidil - pharmacology; Potassium Channel Blockers - pharmacology; Potassium Channels - drug effects; Potassium Channels - metabolism; Protein Synthesis Inhibitors - pharmacology; Rats; rotenone; Rotenone - pharmacology; Uncoupling Agents - pharmacology; Vasodilator Agents - pharmacology; Xanthine - pharmacology; Xanthine Oxidase - pharmacology
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.10309

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 FeSO4 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.