Modulation of mitochondrial respiratory function and ROS production by novel benzopyran analogues
| Autor: | István Baczkó, Alexandra Petrus, Lavinia Noveanu, Oana Duicu, Norbert Jost, Adrian Sturza, Danina Muntean, Maria D. Dănilă, Loránd Kiss |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Physiology Cellular respiration Cell Respiration Oxidative phosphorylation Mitochondrion Mitochondria Heart Oxidative Phosphorylation chemistry.chemical_compound KATP Channels Physiology (medical) medicine Animals Benzopyrans Respiratory function Pharmacology Cardioprotection chemistry.chemical_classification Reactive oxygen species Dose-Response Relationship Drug Molecular Structure Chemistry Hydrogen Peroxide General Medicine medicine.disease Rats Benzopyran Biochemistry Hydroxy Acids Reactive Oxygen Species Decanoic Acids Reperfusion injury |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 93:811-818 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/cjpp-2015-0041 |
| Popis: | 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 mKATPopener, on mitochondrial respiration and reactive oxygen species (ROS) production in isolated rat heart mitochondria. Mitochondrial respiratory function was assessed by high-resolution respirometry, and H2O2production 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 mKATPinhibitor. 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 H2O2release. 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. |
| Databáze: | OpenAIRE |
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