Properties of Pervanadate and Permolybdate

Abstract

Pervanadate and permolybdate are irreversible protein-tyrosine phosphatase inhibitors, with IC 50 values of 0.3 and 20 M, respectively, in intact cells. Maximal inhibition was obtained within 1 min at higher concentrations of the compounds. They induced prominent changes in the phosphorylation status of the gap junction protein, connexin43. These effects were utilized as model systems to assess the stability and inactivation of the compounds. Although the concentrated stock solutions were relatively stable, the diluted compounds were unstable. The biological activity had decreased to 20 -30% after 6 h of incubation in a phosphate buffer, 1 h in phosphate buffer with 10% fetal calf serum, and 1-3 minutes in culture medium. Thiols reacted rapidly with the compounds and inactivated them (initial reaction rates with cysteine: permolybdate > pervanadate > H 2 O 2 ). Catalase inactivated the compounds, and permolybdate was the more sensitive. The cells inactivated permolybdate faster than pervanadate. Cellular inactivation of permolybdate, and to a lesser degree pervanadate, appeared to be partly dependent on catalase and thiols. However, a general decrease in cellular thiols was not the mediator of the biological effects of pervanadate or permolybdate. Mathematical modeling of the thiol reactivity suggested that monoperoxovanadate at maximum could possess 20% of the biological activity of diperoxovanadate.

Phenylethyl Isothiocyanate Induces Apoptotic Signaling via Suppressing Phosphatase Activity against c-Jun N-terminal Kinase

“…To examine this possibility, we studied the pattern of proteintyrosine phosphorylation in PEITC-treated LNCaP cells. Unlike nonspecific phosphatase inhibitor pervanadate (52), which induced a wide spectrum of protein-tyrosine phosphorylation (Fig. 8F), PEITC induced a limited and distinct pattern of protein-tyrosine phosphorylation (with apparent molecular masses of 185, 75, 43 kDa, as indicated by asterisks from top to bottom, Fig.…”

Characterisation of the PTEN inhibitor VO-OHpic

“…Vanadium complexes have the ability to inhibit phosphatases in a reversible [23][24][25] or irreversible fashion [26,27]. Prior to any further characterisation, the reversibility of the The results are the average ± the standard deviations of three independent experiments.…”

Identification of Protein Tyrosine Phosphatases and Dual-Specificity Phosphatases in Mammalian Spermatozoa and Their Role in Sperm Motility and Protein Tyrosine Phosphorylation1

“…To investigate if tyrosine phosphatases also have a role in the regulation of protein tyrosine phosphorylation in boar spermatozoa, we used pervanadate, a potent and cell-permeant inhibitor of PTPs and DSPs [44,45], and evaluated its effect in tyrosine phosphorylation of proteins in capacitated and noncapacitated spermatozoa. Incubation of boar spermatozoa with 100 lM pervanadate for the last 60 min of incubation in TBM (total incubation time, 180 min) caused a marked increase in tyrosine phosphorylation of at least six proteins.…”

“…hydroperoxide) is a membrane-permeable derivative of Na 3 VO 4 [44,45]. A 50 mM pervanadate solution was prepared by mixing an equivalent concentration (100 mM) of Na 3 VO 4 and hydrogen peroxide, followed by a 15-min incubation at room temperature in darkness.…”