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

Decameric vanadate species (V10) inhibit the rate and the extent of G-actin polymerization with an IC50 of 68 +/- 22 mu M and 17 +/- 2 mu M, respectively, whilst they induce F-actin de polymerization at a lower extent. On contrary, no effect on actin polymerization and depolymerization was detected for 2 mM concentration of metavanadate solution that contains ortho and metavanadate species, as observed by combining kinetic with V-51 NMR spectroscopy studies. Although at 25 degrees C, decameric vanadate (10 mu M) is unstable in the assay medium, and decomposes following a first-order kinetic, in the presence of G-actin (up to 8 mu M), the half-life increases 5-fold (from 5 to 27 h). However, the addition of ATP (0.2 mM) in the medium not only prevents the inhibition of G-actin polymerization by V 10 but it also decreases the half-life of decomposition of decameric vanadate species from 27 to 10 h. Decameric vanadate is also stabilized by the sarcoplasmic reticulum vesicles, which raise the half-life time from 5 to 18 It whereas no effects were observed in the presence of phosphatidylcholine liposomes, myosin or G-actin alone. It is proposed that the decavanadate interaction with G-actin, favored by the G-actin polymerization, stabilizes decameric vanadate species and induces inhibition of G-actin polymerization. Decameric vanadate stabilization by cytoskeletal and transmembrane proteins can account, at least in part, for decavanadate toxicity reported in the evaluation of vanadium (V) effects in biological systems. (c) 2006 Elsevier Inc. All rights reserved.