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Opening mitoKATP increases superoxide generation from complex I of the electron transport chain.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Andrukhiv, Anastasia Costa, Alexandre Dias Tavares West, Ian C. Garlid, Keith D. |
| Copyright Year | 2006 |
| Abstract | Opening the mitochondrial ATP-sensitive K(+) channel (mitoK(ATP)) increases levels of reactive oxygen species (ROS) in cardiomyocytes. This increase in ROS is necessary for cardioprotection against ischemia-reperfusion injury; however, the mechanism of mitoK(ATP)-dependent stimulation of ROS production is unknown. We examined ROS production in suspensions of isolated rat heart and liver mitochondria, using fluorescent probes that are sensitive to hydrogen peroxide. When mitochondria were treated with the K(ATP) channel openers diazoxide or cromakalim, their ROS production increased by 40-50%, and this effect was blocked by 5-hydroxydecanoate. ROS production exhibited a biphasic dependence on valinomycin concentration, with peak production occurring at valinomycin concentrations that catalyze about the same K(+) influx as K(ATP) channel openers. ROS production decreased with higher concentrations of valinomycin and with all concentrations of a classical protonophoretic uncoupler. Our studies show that the increase in ROS is due specifically to K(+) influx into the matrix and is mediated by the attendant matrix alkalinization. Myxothiazol stimulated mitoK(ATP)-dependent ROS production, whereas rotenone had no effect. This indicates that the superoxide originates in complex I (NADH:ubiquinone oxidoreductase) of the electron transport chain. |
| Starting Page | 298 |
| Ending Page | 300 |
| Page Count | 3 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ajpheart.physiology.org/content/ajpheart/291/5/h2067.full.pdf |
| PubMed reference number | 16798828v1 |
| Volume Number | 291 |
| Issue Number | 5 |
| Journal | American journal of physiology. Heart and circulatory physiology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 5-hydroxydecanoate Adenosine Triphosphate Alkalinization Cromakalim Diazoxide Hydrogen Peroxide Mitochondria, Liver Myocytes, Cardiac NADH dehydrogenase (ubiquinone) Peroxides Potassium Reactive Oxygen Species Reperfusion Injury Reperfusion Therapy Rotenone Superoxides Suspensions Ubiquinone Valinomycin electron transport chain mitochondrial K(ATP) channel myxothiazol |
| Content Type | Text |
| Resource Type | Notes |
