Modulation of mitochondrial respiratory function and ROS production by novel benzopyran analogues

Canadian Journal of Physiology and Pharmacology
Alexandra PetruşNorbert Jost

Abstract

A substantial body of evidence indicates that pharmacological activation of mitochondrial ATP-sensitive potassium channels (mKATP) in the heart is protective in conditions associated with ischemia/reperfusion injury. Several mechanisms have been postulated to be responsible for cardioprotection, including the modulation of mitochondrial respiratory function. The aim of the present study was to characterize the dose-dependent effects of novel synthetic benzopyran analogues, derived from a BMS-191095, a selective mKATP opener, on mitochondrial respiration and reactive oxygen species (ROS) production in isolated rat heart mitochondria. Mitochondrial respiratory function was assessed by high-resolution respirometry, and H2O2 production was measured by the Amplex Red fluorescence assay. Four compounds, namely KL-1487, KL-1492, KL-1495, and KL-1507, applied in increasing concentrations (50, 75, 100, and 150 μmol/L, respectively) were investigated. When added in the last two concentrations, all compounds significantly increased State 2 and 4 respiratory rates, an effect that was not abolished by 5-hydroxydecanoate (5-HD, 100 μmol/L), the classic mKATP inhibitor. The highest concentration also elicited an important decrease of the oxid...Continue Reading

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Citations

Feb 20, 2016·Current Opinion in Pharmacology·James W WaltersNalini Santanam
May 21, 2016·Oxidative Medicine and Cellular Longevity·Danina M MunteanCristian Mornoș

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