Decavanadate induces mitochondrial membrane depolarization and inhibits oxygen consumption

Abstract

Decavanadate induced rat liver mitochondrial depolarization at very low concentrations, half-depolarization with 39 nM decavanadate, while it was needed a 130-fold higher concentration of monomeric vanadate (5 lM) to induce the same effect. Decavanadate also inhibits mitochondrial repolarization induced by reduced glutathione in vitro, with an inhibition constant of 1 lM, whereas no effect was observed up to 100 lM of monomeric vanadate. The oxygen consumption by mitochondria is also inhibited by lower decavanadate than monomeric vanadate concentrations, i.e. 50% inhibition is attained with 99 nM decavanadate and 10 lM monomeric vanadate. Thus, decavanadate is stronger as mitochondrial depolarization agent than as inhibitor of mitochondrial oxygen consumption. Up to 5 lM, decavanadate does not alter mitochondrial NADH levels nor inhibit neither F O F 1 -ATPase nor cytochrome c oxidase activity, but it induces changes in the redox steady-state of mitochondrial b-type cytochromes (complex III). NMR spectra showed that decameric vanadate is the predominant vanadate species in decavanadate solutions. It is concluded that decavanadate is much more potent mitochondrial depolarization agent and a more potent inhibitor of mitochondrial oxygen consumption than monomeric vanadate, pointing out the importance to take into account the contribution of higher oligomeric species of vanadium for the biological effects of vanadate solutions.

Decavanadate: a journey in a search of a role

“…17,30-53 The formation of reactive oxygen species (ROS) induced by vanadium in biological systems may involve Fenton-like reactions 48 , vanadate bioreduction mediated by reduced glutathione (GSH), flavoenzymes or nicotinamide adenine dinucleotide, reduced form (NADH), and nicotinamide adenine dinucleotide phosphate, reduced form (NADPH), oxidases 49, 50 or interaction with mitochondria. 20, 30 Mitochondria, a potential producer of ROS, have recently been suggested as a potential target of vanadium, decavanadate or monomeric vanadate, since mitochondrial membrane depolarization is a key event in vanadate-induced necrotic cell death of cardiomyocytes. 20 Moreover, efforts have been dedicated in recent years to learn more about the characterization of effects in bone-derived systems by vanadium, namely signalling pathways, extracellular matrix inhibition and inhibition of alakaline phosphatase activity, that impact cell differentiation.…”

Vanadium induces liver toxicity through reductive activation by glutathione and mitochondrial dysfunction

“…On the other hand, V 5+ reacted with thiols to produce V 4+ and thiyl radicals [7]. Several studies have associated V 5+ -toxicity with its capacity to induce the formation of reactive oxygen species (ROS), probably by interacting with mitochondrial redox centers [8][9][10]. It is generally known that the GSH-related thiols participate in many important biological reactions, including the protection of cell membranes against oxidative damage.…”

Chemical, Biochemical, and Biological Behaviors of Vanadate and Its Oligomers

“…In vitro studies showed that decavanadate is stronger than vanadate in inducing membrane depolarization and inhibiting oxygen consumption to isolated hepatic and cardiac mitochondria (Soares et al 2007a). …”