Modulation of mitochondrial respiratory function and ROS production by novel benzopyran analogues
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, inc...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2015
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| Sorozat: | CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
93 No. 9 |
| doi: | 10.1139/cjpp-2015-0041 |
| mtmt: | 2937141 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/9909 |
| Tartalmi kivonat: | 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 mumol/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 mumol/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 mumol/L for KL-1487, KL-1492, and KL-1495, and the concentration of 150 mumol/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. |
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| Terjedelem/Fizikai jellemzők: | 811-818 |
| ISSN: | 0008-4212 |