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- W2068273663 abstract "Some TCA cycle enzymes, like aconitase, are more susceptible to ischemia reperfusion (IR) injury. Ranolazine (RAN) is cardioprotective against IR injury. It is a late Na+ current blocker that may also limit lipid peroxidation and complex I activity. It is unknown if RAN alters the redox state of Fe-S clusters or free radical generation (FRG) to underlie its protection. Here we examined how IR injury affects FRG and Fe-S clusters of aconitase and succinate dehydrogenase, using electron paramagnetic resonance (EPR), and if RAN alters these effects. Guinea pig hearts (n=8) were isolated and perfused with Krebs Ringer buffer and exposed to: a) control, b) 30 min global ischemia, c) 10 μM RAN for 10 min just before ischemia, or d) ischemia and 10 min reperfusion. Hearts were immediately ground in liquid N2 and packed into EPR tubes. We examined changes in signal intensity in liquid He (10°K) of assigned g=2.016 (aconitase 3Fe-4S), g=1.93 (succinate dehydrogenase 2Fe-2S), g=2.006 (free radical), and g=6.0 (Fe group of cytochrome c). Versus time control (100%), the signal for aconitase Fe-S at the end of ischemia was 46%, suggesting oxidative damage; this was partially restored by 10 min reperfusion to 91% and after I+RAN treatment to 55% of control. Signal intensity for succinate dehydrogenase was unaltered by IR or RAN+IR. The presumptive ubisemiquinone radical signal increased 19% after ischemia, suggesting increased FRG, but only by 4% at 10 min reperfusion. I+RAN treatment decreased the signal by 19%. The signal for cytochrome c (g=6.0) increased 730% after IR, but was only 81% after I+RAN. These data suggest that RAN treatment partially restores electron flow through some Fe-S centers and reduces FRG, which may partially underlie its cardioprotective effects." @default.
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- W2068273663 date "2010-01-01" @default.
- W2068273663 modified "2023-10-14" @default.
- W2068273663 title "Free Radical Generation and Electron Flux in Mitochondrial Fe-S Centers During Cardiac Injury; Changes with Mitochondrial Protective Drug Ranolazine" @default.
- W2068273663 doi "https://doi.org/10.1016/j.bpj.2009.12.2158" @default.
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