Stimulation of mitochondrial ATP synthase activity - a new diazoxide-mediated mechanism of cardioprotection.

Article Details

Citation

Copy to clipboard

Jasova M, Kancirova I, Murarikova M, Farkasova V, Waczulikova I, Ravingerova T, Ziegelhoffer A, Ferko M

Stimulation of mitochondrial ATP synthase activity - a new diazoxide-mediated mechanism of cardioprotection.

Physiol Res. 2016 Sep 19;65 Suppl 1:S119-27. doi: 10.33549/physiolres.933411.

PubMed ID

27643934 [ View in PubMed

]

Abstract

Pharmacological preconditioning by diazoxide and a model of experimental streptozotocin-induced acute diabetes mellitus (STZ-DM) provided similar levels of cardioprotection assessed as limiting myocardial infarct size. The aim was to explore the possibility of existence of another in vitro mechanism, which could be contributory to cardioprotection mediated by diazoxide treatment. Mitochondrial membrane fluidity and ATP synthase activity in isolated heart mitochondria were determined under the influence of two factors, STZ-DM condition and treatment with diazoxide. Both factors independently increased the ATP synthase activity (p<0.05), as no interaction effect was observed upon the combination of STZ-DM with diazoxide. On the other hand, the mitochondrial membrane fluidity was significantly increased by STZ-DM only; no significant main effect for diazoxide was found. Based on the results from measurements of enzyme kinetics, we assume a direct interaction of diazoxide with the molecule of ATP synthase stimulated its activity by noncompetitive activation. Our present work revealed, for the first time, that cardioprotection induced by diazoxide may not be caused exclusively by mitochondrial K(ATP) opening, but presumably also by a direct interaction of diazoxide with ATP synthase, although the mechanisms for achieving this activation cannot be fully delineated.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Diazoxide	Mitochondrial ATP synthase F1 domain (Protein Group)	Protein group	Humans	Unknown	Inhibitor	Details