Decavanadate effects in biological systems

Abstract

Vanadium biological studies often disregarded the formation of decameric vanadate species known to interact, in vitro, with high-affinity with many proteins such as myosin and sarcoplasmic reticulum calcium pump and also to inhibit these biochemical systems involved in energy transduction. Moreover, very few in vivo animal studies involving vanadium consider the contribution of decavanadate to vanadium biological effects. Recently, it has been shown that an acute exposure to decavanadate but not to other vanadate oligomers induced oxidative stress and a different fate in vanadium intracellular accumulation. Several markers of oxidative stress analyzed on hepatic and cardiac tissue were monitored after in vivo effect of an acute exposure (12, 24 h and 7 days), to a sub-lethal concentration (5 mM; 1 mg/kg) of two vanadium solutions (''metavanadate'' and ''decavanadate''). It was observed that ''decavanadate'' promote different effects than other vanadate oligomers in catalase activity, glutathione content, lipid peroxidation, mitochondrial superoxide anion production and vanadium accumulation, whereas both solutions seem to equally depress reactive oxygen species (ROS) production as well as total intracellular reducing power. Vanadium is accumulated in mitochondria in particular when ''decavanadate'' is administered. These recent findings, that are now summarized, point out the decameric vanadate species contributions to in vivo and in vitro effects induced by vanadium in biological systems.

Decavanadate interactions with actin: Inhibition of G-actin polymerization and stabilization of decameric vanadate

“…Recent work from our laboratory [20][21][22][23] demonstrated that an acute exposure to decameric vanadate species, but not exposure to monomeric vanadate, induces changes on vanadium accumulation and in overall stress markers. Altogether, these observations reveal that decameric vanadate plays an important role in the evaluation of vanadium (V) toxicity in biological systems [17].…”

“…By inhibiting G-actin polymerization, decameric vanadate eventually prevents microfilaments formation and F-actin stimulation of myosin ATPase activity. However, before attempting to understand the effects promoted by each individual vanadate species that may occur in the reaction medium, it is of primary importance to characterize precisely the vanadate solutions and the interactions with the system by using 51 V NMR spectroscopy [17].…”

“…Time course of G-actin (8 lM) polymerization (in Tris 2 mM, CaCl 2 0.2 mM, ATP 10 lM, pH 7.5), monitored by light-scattering at 546 nm, 25°C, in the absence (a) and in the presence of 4 mM (b) and 8 mM (c) of decavanadate (total vanadate concentration) added to the buffer just before starting the polymerization (with KCl 100 mM, MgCl 2 2 mM) at 25°C. spectroscopy [17,36]. Only for metavanadate concentrations at the micromolar range, orthovanadate species are exclusively present [14].…”

“…To this end a combination of biochemical kinetic studies with 51 V NMR spectroscopy has proven to be very valuable [12,14,16], as it allows correlating inhibitory effects with specific vanadate species distribution in solution [12,14]. Therefore, it is of primary importance to characterize precisely the vanadate species and the interactions with the system before attempting to understand the promoted effects [17].…”

Ion pumps as biological targets for decavanadate

“…49 Furthermore, decavanadate, 50 and compounds containing decavanadate 51 have been reported to lower glycemic levels, 50,51 and to normalize plasma lipid profiles. 51 Due to the ability of V 10 to interfere with several biological processes, such as calcium homeostasis, muscle contraction and oxidative stress, 8,54,55 not only in vitro but also in vivo, 52,53 decavanadate has recently been associated with the treatment of Leishmaniosis. 56 In this and probably in many other cases the mechanism of action of decavanadate progresses via the inhibition of the E1-E2 Ca 2+ -ATPases.…”