Petrus 2015 Can J Physiol Pharmacol
|Petruş A, Duicu OM, Sturza A, Noveanu L, Kiss L, Dănilă M, Baczkó I, Muntean DM, Jost N (2015) Modulation of mitochondrial respiratory function and ROS production by novel benzopyran analogues. Can J Physiol Pharmacol 93:811-8.|
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 oxidative phosphorylation in a K(+) independent manner. Both concentrations of 100 and 150 μmol/L for KL-1487, KL-1492, and KL-1495, and the concentration of 150 μmol/L for KL-1507, respectively, mitigated the mitochondrial H2O2 release. In isolated rat heart mitochondria, the novel benzopyran analogues act as protonophoric uncouplers of oxidative phosphorylation and decrease the generation of reactive oxygen species in a dose-dependent manner.
• Keywords: Rat heart mitochondria, Benzopyran analogues, Protonophores, Uncoupling, Hydrogen peroxide
• O2k-Network Lab: RO Timisoara Muntean DM
Labels: MiParea: Respiration, Pharmacology;toxicology
Stress:Ischemia-reperfusion Organism: Rat Tissue;cell: Heart Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET Pathway: N, ROX HRR: Oxygraph-2k