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

Alexandra Petruş, Oana M. Duicu, Adrian Sturza, Lavinia Noveanu, L. Kiss, Maria Dănilă, I. Baczkó, Danina M. Muntean, N. Jost

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)811-818
Number of pages8
JournalCanadian Journal of Physiology and Pharmacology
Volume93
Issue number9
DOIs
Publication statusPublished - Apr 15 2015

Fingerprint

Benzopyrans
Heart Mitochondria
Oxidative Phosphorylation
Reactive Oxygen Species
KATP Channels
Respiratory Rate
Reperfusion Injury
Respiration
Fluorescence
Pharmacology
BMS 191095
5-hydroxydecanoic acid

Keywords

  • Benzopyran analogues
  • Hydrogen peroxide
  • Protonophores
  • Rat heart mitochondria
  • Uncoupling

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

Cite this

Modulation of mitochondrial respiratory function and ROS production by novel benzopyran analogues. / Petruş, Alexandra; Duicu, Oana M.; Sturza, Adrian; Noveanu, Lavinia; Kiss, L.; Dănilă, Maria; Baczkó, I.; Muntean, Danina M.; Jost, N.

In: Canadian Journal of Physiology and Pharmacology, Vol. 93, No. 9, 15.04.2015, p. 811-818.

Research output: Contribution to journalArticle

Petruş, Alexandra ; Duicu, Oana M. ; Sturza, Adrian ; Noveanu, Lavinia ; Kiss, L. ; Dănilă, Maria ; Baczkó, I. ; Muntean, Danina M. ; Jost, N. / Modulation of mitochondrial respiratory function and ROS production by novel benzopyran analogues. In: Canadian Journal of Physiology and Pharmacology. 2015 ; Vol. 93, No. 9. pp. 811-818.
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