Modulation of mitochondrial respiratory function and ROS production by novel benzopyran analogues
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Tartalom: http://real.mtak.hu/31573/
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published

Type = Article
Cím:
Modulation of mitochondrial respiratory function and ROS production by novel benzopyran analogues
Létrehozó:
Petrus, Alexandra
Duicu, Oana
Sturza, Adrian
Noveanu, Lavinia
Kiss, Loránd
Danila, Maria
Bazckó, István
Muntean, Danina
Jost, Norbert
Dátum:
2015
Téma:
RM Therapeutics. Pharmacology / terápia, gyógyszertan
Tartalmi leírás:
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 ?mol/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 ?mol/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 ?mol/L for
KL-1487, KL-1492, and KL-1495, and the concentration of 150 ?mol/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.
Típus:
Article
PeerReviewed
Formátum:
text
Azonosító:
Petrus, Alexandra and Duicu, Oana and Sturza, Adrian and Noveanu, Lavinia and Kiss, Loránd and Danila, Maria and Bazckó, István and Muntean, Danina and Jost, Norbert (2015) Modulation of mitochondrial respiratory function and ROS production by novel benzopyran analogues. CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 93. pp. 811-818. ISSN 0008-4212
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