| Title | Opening of the mitoK(ATP) channel and decoupling of mitochondrial complex II and III contribute to the suppression of myocardial reperfusion hyperoxygenation. | | Author(s) | Liu B, Zhu X, Chen CL, Hu K, Swartz HM, Chen YR, He G | | Institution | The Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, 43210, USA. | | Source | Mol Cell Biochem 2009 Oct 23. | | Abstract | Diazoxide, a mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel opener, protects the heart from ischemia-reperfusion injury. Diazoxide also inhibits mitochondrial complex II-dependent respiration in addition to its preconditioning effect. However, there are no prior studies of the role of diazoxide on post-ischemic myocardial oxygenation. In the current study, we determined the effect of diazoxide on the suppression of post-ischemic myocardial tissue hyperoxygenation in vivo, superoxide (O(2) (-*)) generation in isolated mitochondria, and impairment of the interaction between complex II and complex III in purified mitochondrial proteins. It was observed that diazoxide totally suppressed the post-ischemic myocardial hyperoxygenation. With succinate but not glutamate/malate as the substrate, diazoxide significantly increased ubisemiquinone-dependent O(2) (-*) generation, which was not blocked by 5-HD and glibenclamide. Using a model system, the super complex of succinate-cytochrome c reductase (SCR) hosting complex II and complex III, we also observed that diazoxide impaired complex II and its interaction with complex III with no effect on complex III. UV-visible spectral analysis revealed that diazoxide decreased succinate-mediated ferricytochrome b reduction in SCR. In conclusion, our results demonstrated that diazoxide suppressed the in vivo post-ischemic myocardial hyperoxygenation through opening the mitoK(ATP) channel and ubisemiquinone-dependent O(2) (-*) generation via inhibiting mitochondrial complex II-dependent respiration. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19851835 |
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