Difference between revisions of "Petrus 2015 Can J Physiol Pharmacol"
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|journal=Can J Physiol Pharmacol | |journal=Can J Physiol Pharmacol | ||
|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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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. | |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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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= | |keywords=Rat heart mitochondria, Benzopyran analogues, Protonophores, Uncoupling, Hydrogen peroxide | ||
|mipnetlab=RO Timisoara Muntean DM | |mipnetlab=RO Timisoara Muntean DM | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration, Pharmacology;toxicology | ||
|organism=Rat | |organism=Rat | ||
|tissues=Heart | |tissues=Heart | ||
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|substratestates=CI, ROX | |substratestates=CI, ROX | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional= | |additional=Amplex Red, 2015-12 | ||
}} | }} |
Revision as of 12:50, 23 March 2016
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. |
Petrus A, Duicu OM, Sturza A, Noveanu L, Kiss L, Danila M, Baczko I, Muntean DM, Jost N (2015) Can J Physiol Pharmacol
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, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
Amplex Red, 2015-12