Biological Effects of Decavanadate: Muscle Contraction, In Vivo Oxidative Stress, and Mitochondrial Toxicity

Abstract

Decameric vanadate species (V10) can be formed at physiological pH values in vanadate solutions presumably containing only monomeric vanadate species (VI). Sarcoplasmic reticulum Ca 2+ -ATPase and myosin are known to interact with decameric vanadate species. V10 interaction with myosin is favored by conformational changes that take place in myosin during the catalytic cycle. Apparently, V10 operates at a different protein state in comparison with monomeric vanadate (VI) that mimics the protein at the hydrolysis transition state. V10 also clearly differs from V1, by inhibiting sarcoplasmic reticulum calcium accumulation in non-damage native vesicles, besides affecting calcium efflux associated with ATP synthesis and proton ejection associated with ATP hydrolysis. Recently reported studies referred that V10 is stabilized by actin during the process of the protein polymerization since the decomposition half-life time increases from 5 to 27 hours, suggesting that the interaction is also supported by a protein conformation induced during ATP hydrolysis followed by the formation of protein filaments. Besides affecting muscle contraction and its regulation, V10, as low as 100 nM, inhibits 50% of oxygen consumption in mitochondria, pointing that this organelle is a potential cellular target for V10, while a 100-fold higher concentration of V1 (10 μM) is needed to induce the same effect. Furthermore, in vivo studies have shown that following an acute exposure, decavanadate induced different changes, when compared with vanadate, on oxidative stress markers, vanadium intracellular accumulation as well as in lipid peroxidation. Putting it all together, it is suggested that the biological effects of decameric vanadate species contribute, at least in part, to the understanding of the versatility of vanadium biochemistry.