Recent advances into vanadyl, vanadate and decavanadate interactions with actin

Abstract

Although the number of papers about ''vanadium'' has doubled in the last decade, the studies about ''vanadium and actin'' are scarce. In the present review, the effects of vanadyl, vanadate and decavanadate on actin structure and function are compared. Decavanadate 51 V NMR signals, at À516 ppm, broadened and decreased in intensity upon actin titration, whereas no effects were observed for vanadate monomers, at À560 ppm. Decavanadate is the only species inducing actin cysteine oxidation and vanadyl formation, both processes being prevented by the natural ligand of the protein, ATP. Vanadyl titration with monomeric actin (G-actin), analysed by EPR spectroscopy, reveals a 1 : 1 binding stoichiometry and a K d of 7.5 mM À1 . Both decavanadate and vanadyl inhibited G-actin polymerization into actin filaments (F-actin), with a IC 50 of 68 and 300 mM, respectively, as analysed by light scattering assays, whereas no effects were detected for vanadate up to 2 mM. However, only vanadyl (up to 200 mM) induces 100% of G-actin intrinsic fluorescence quenching, whereas decavanadate shows an opposite effect, which suggests the presence of vanadyl high affinity actin binding sites. Decavanadate increases (2.6-fold) the actin hydrophobic surface, evaluated using the ANSA probe, whereas vanadyl decreases it (15%). Both vanadium species increased the e-ATP exchange rate (k = 6.5 Â 10 À3 s À1 and 4.47 Â 10 À3 s À1 for decavanadate and vanadyl, respectively). Finally, 1 H NMR spectra of G-actin treated with 0.1 mM decavanadate clearly indicate that major alterations occur in protein structure, which are much less visible in the presence of ATP, confirming the preventive effect of the nucleotide on the decavanadate interaction with the protein. Putting it all together, it is suggested that actin, which is involved in many cellular processes, might be a potential target not only for decavanadate but above all for vanadyl. By affecting actin structure and function, vanadium can regulate many cellular processes of great physiological significance.

Vanadium and proteins: Uptake, transport, structure, activity and function

“…Globally, the biological role of decavanadate may partly result by its capacity to interact with actin and to affect several biological processes where actin may be involved. It was concluded that[493]: (i) V10 and V IV O 2+ inhibit actin polymerization at M concentrations; (ii) only interaction of V 10 with actin induces cysteine oxidation and formation of V IV , these effects being prevented by ATP; (iii) decavanadate and V IV O 2+ induce actin conformational changes affecting the protein ATP binding site; (iv) actin has high affinity binding sites for V IV O 2+ .…”

Characterization of decavanadate and decaniobate solutions by Raman spectroscopy

“…26 Decavanadate was observed to induce protein cysteine oxidation and vanadyl formation in the presence of SR Ca 2+ -ATPase and actin, whereas no effects were observed on incubation with monomeric vanadate. 7,10,27 This reactivity of V 10 was attributed to the involvement of cysteines at the V 10 -binding site, as well as the participation of reduced vanadyl (V IV -containing) species in the enzymatic inhibition process. 10 It is known that actin, in common with other proteins such as transferrin and albumin, contains a high affinity binding site for vanadyl.…”

“…10 It is known that actin, in common with other proteins such as transferrin and albumin, contains a high affinity binding site for vanadyl. 7 Decavanadate interactions with certain proteins can thus lead to vanadyl protein binding, although the participation of vanadyl in the process is yet to be clarified.…”

“…[1][2][3][4] Decavanadate is a homoleptic isopolyoxovanadate that interacts with high affinity with several proteins such as myosin, actin, and Ca 2+ -ATPase, thus affecting a range of cellular processes, including calcium homeostasis, muscle contraction, cytoskeleton dynamics and mitochondrial oxygen consumption. [4][5][6][7][8][9][10][11] Furthermore, the antidiabetic, anti-virus, anti-bacterial and anti-tumor activities of V 10 and vanadate compounds are attracting increasing interest. [12][13][14][15][16][17][18] Decavanadate also exhibits insulin-mimetic behavior, and it was shown that, upon incubation with decavanadate, rat adipocytes accumulate much more glucose than with well-established mimetic agents such as BMOV.…”

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

“…The effect on G-actin polymerization is important in maintaining the integrity of cytoskeleton and also in muscle contraction. The interaction of decavanadate with G-actin was described as follows: decavanadate oxidizes cysteine thiol group with concurrent formation of vanadyl ions at first, and then the vanadyl ions bind to actin, causes conformation change, and finally inhibition of G-actin polymerization (Aureliano 2011;Ramos et al 2006Ramos et al , 2012. Differing from V 10 , monovanadate does not interact with the cysteine thiol and acts merely as a phosphate analogue.…”