Redox properties of the adenoside triphosphate-sensitive K+ channel in brain mitochondria.
Brain mitochondrial ATP-sensitive K+ channel (mitoK(ATP)) opening by diazoxide protects against ischemic damage and excitotoxic cell death. Here we studied the redox properties of brain mitoK(ATP) . MitoK(ATP) activation during excitotoxicity in cultured cerebellar granule neurons prevented the accumulation of reactive oxygen species (ROS) and cell death. Furthermore, mitoK(ATP) activation in isolated brain mitochondria significantly prevented H2O2 release by these organelles but did not change Ca2+ accumulation capacity. Interestingly, the activity of mitoK(ATP) was highly dependent on redox state. The thiol reductant mercaptopropionylglycine prevented mitoK(ATP) activity, whereas exogenous ROS activated the channel. In addition, the use of mitochondrial substrates that led to higher levels of endogenous mitochondrial ROS release closely correlated with enhanced K+ transport activity through mitoK(ATP). Altogether, our results indicate that brain mitoK(ATP) is a redox-sensitive channel that controls mitochondrial ROS release.
Fornazari
Maynara
M
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
de Paula
Juliana G
JG
Castilho
Roger F
RF
Kowaltowski
Alicia J
AJ
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D003981:Diazoxide / Q000494:pharmacology; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D008933:Mitochondrial Swelling / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D008625:Tiopronin / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D054086:KATP Channels; D017382:Reactive Oxygen Species; D016202:N-Methylaspartate; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D008625:Tiopronin; D007770:L-Lactate Dehydrogenase; D003981:Diazoxide; D010100:Oxygen; D002118:Calcium