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PubMed1991

Nonreductive interaction of vanadate with an enzyme containing a thiol group in the active site: glycerol-3-phosphate dehydrogenase.

The inhibitory effects of vanadium(V) were determined on the oxidation of glycerol 3-phosphate (G3P) catalyzed by glycerol-3-phosphate dehydrogenase (G3PDH), an enzyme with a thiol group in the active site. G3PDH from rabbit muscle was inhibited by vanadate, and the active inhibiting species were found to be the vanadate dimer and/or tetramer. The dimer was a sufficiently weak inhibitor at pH 7.4 with respect to G3P; the tetramer could account for all the observed inhibition. The tetramer was a competitive inhibitor with respect to G3P with a Ki of 0.12 mM. Both the dimer and tetramer were noncompetitive inhibitors at pH 7.4 with respect to NAD with Ki's of 0.36 mM and 0.67 mM. G3PDH inhibited by vanadate was reactivated when EDTA complexed the vanadate. The reactivation occurred even after extended periods of incubation of G3PDH and vanadate, suggesting that the inhibition is reversible despite the thiol group in the active site. Analogous reactivation is also observed with glyceraldehyde-3-phosphate dehydrogenase (Gly3PDH). Gly3PDH is an enzyme that previously had been reported to undergo redox chemistry with vanadate. The work described in this paper suggests vanadate will not necessarily undergo redox chemistry with enzymes containing thiol groups exposed on the surface of the protein.

Animals↗
PubMed1997

Induction of AP-1 activity associated with c-Jun and JunB is required for mitogenesis induced by insulin and vanadate in SV40-transformed 3T3T cells.

Insulin and vanadate function as complete mitogens for SV40-transformed murine 3T3T (CSV3-1) cells but not for nontransformed 3T3T cells. Mitogenesis induced by insulin and vanadate in CSV3-1 cells is associated with the induction of the expression of protooncogenes c-jun and junB, two major AP-1 transcription factor components. We now report that both insulin and vanadate induce a significant increase in AP-1 DNA binding activity in CSV3-1 cells but not in 3T3T cells. Gel supershift assays and Western blot analysis using specific antibodies demonstrate that the increased AP-1 binding activity induced by insulin and vanadate in CSV3-1 cells is primarily contributed by an increase in the expression of c-Jun and JunB protein levels. Furthermore, treatment of CSV3-1 cells with antisense oligodeoxyribonucleotides to c-jun or to junB blocks insulin- and vanadate-induced mitogenesis whereas antisense junD oligomers have no inhibitory effects. These results therefore demonstrate that the induction of AP-1 binding activity associated with c-Jun and JunB is required for insulin- and vandate-induced mitogenesis in SV40-transformed murine 3T3T cells. Additional data presented in this paper show that JunD/AP-1 binding activity, which is thought to play a negative role in regulating cell proliferation, is also slightly induced following insulin and vanadate stimulation in CSV3-1 cells. Nevertheless, the ratio of proliferation promoting c-Jun/AP-1 and JunB/AP-1 binding activities to proliferation inhibiting JunD/AP-1 binding activity is significantly increased following insulin and vanadate stimulation. These results therefore support the concept that modulation of the balance of positive Jun/AP-1 and negative Jun/AP-1 activities is important in regulating cell proliferation.

3T3 Cells↗
PubMed2000

Effect of vanadate and insulin on glucose transport in isolated adult rat cardiomyocytes.

It is now widely accepted that insulin stimulation of glucose uptake by muscle cells is due to the activation of protein kinase B, leading to the recruitment of glucose transporter proteins from an intracellular compartment to the plasma membrane. Vanadate is a protein tyrosine phosphatase (PTP) inhibitor and a known insulin mimetic agent. Vanadate causes an increase of glucose transport in various tissues, but the mechanism of stimulation is not clearly understood. Hence in the present study, we have compared the mechanism of 2-deoxy-D-glucose transport induced by vanadate and insulin in isolated rat cardiomyocytes. Vanadate stimulated deoxyglucose transport in a time- and concentration-dependent manner. Insulin (100 nM) and vanadate (5 mM) stimulated 2-deoxy-D-glucose transport on an average by 3- and 2-fold respectively over basal values. The stimulation of glucose transport was accompanied by an activation of protein kinase B (PKB). This study also revealed that the activation of PKB and stimulation of 2-deoxyglucose uptake by vanadate and insulin are inhibited by treatment with wortmannin, a specific inhibitor of phoshatidylinositol 3-kinase (PI 3-kinase). Hence, we conclude that both insulin and vanadate follow the same signalling pathway downstream of PI 3-kinase to stimulate 2-deoxy-D-glucose transport.

Analysis of Variance↗
PubMed1990

Activation of permeabilized HL60 cells by vanadate. Evidence for divergent signalling pathways.

The possible role of tyrosine phosphorylation in the activation of granulocytic HL60 cells was examined using vanadate, a phosphotyrosine phosphatase inhibitor. Treatment of permeabilized cells with micromolar concentrations of vanadate resulted in a substantial accumulation of tyrosine-phosphorylated proteins, detected by immunoblotting. At comparable concentrations, vanadate was also found to elicit an NADPH-dependent burst of oxygen utilization. Actin assembly, studied using 7-nitrobenz-2-oxa-1,3-diazole (NBD)-phallacidin, was similarly stimulated by vanadate, though considerably higher concentrations were required to observe this effect. In contrast with these responses, the secretion of lysozyme was not stimulated by vanadate, nor did vanadate affect calcium-induced secretion. Therefore, accumulation of tyrosine-phosphorylated proteins is associated with stimulation of some, but not all, of the responses characteristic of granulocytic cell activation. This indicates that the effects of vanadate are selective and suggests divergence of the signalling pathways leading to the individual effectors.

Actins↗
PubMed1991

Mechanism of vanadate-induced activation of tyrosine phosphorylation and of the respiratory burst in HL60 cells. Role of reduced oxygen metabolites.

Vanadate induces phosphotyrosine accumulation and activates O2 consumption in permeabilized differentiated HL60 cells. NADPH, the substrate of the respiratory burst oxidase, was found to be necessary not only for the increased O2 consumption, but also for tyrosine phosphorylation. The effect of NADPH was not due to reduction of vanadate to vanadyl. Instead, NADPH was required for the synthesis of superoxide, which triggered the formation of peroxovanadyl [V(4+)-OO] and vanadyl hydroperoxide [V(4+)-OOH]. One or both of these species, rather than vanadate itself, appears to be responsible for phosphotyrosine accumulation and activation of the respiratory burst. Accordingly, the stimulatory effects of vanadate and NADPH were abrogated by superoxide dismutase. Moreover, phosphorylation was activated in the absence of NADPH by treatment with V(4+)-OO and/or V(4+)-OOH, generated by treatment of orthovanadate with KO2 or H2O2 respectively. The main source of the superoxide involved in the formation of V(4+)-OO and V(4+)-OOH is the NADPH oxidase. This was shown by the inhibitory effects of diphenylene iodonium and by the failure of undifferentiated cells, which lack oxidase activity, to undergo tyrosine phosphorylation when treated with vanadate and NADPH. By contrast, exogenously generated V(4+)-OO induced marked phosphorylation in the undifferentiated cells, demonstrating the presence of the appropriate tyrosine kinases and phosphatases. A good correlation was found to exist between induction of tyrosine phosphorylation and activation of the respiratory burst, suggesting a causal relationship. Therefore an amplification cycle appears to exist in cells treated with vanadate, whereby trace amounts of superoxide initiate the formation of V(4+)-OO and/or V(4+)-OOH. These peroxides promote phosphotyrosine formation, most likely by inhibition of tyrosine phosphatases. Accumulation of critical tyrosine-phosphorylated proteins then initiates a respiratory burst, with abundant production of superoxide. The newly formed superoxide catalyses the formation of additional V(4+)-OO and/or V(4+)-OOH, thereby magnifying the response. Since vanadium derivatives are ubiquitous in animal tissues, V(4+)-OO and/or V(4+)-OOH could be formed in vivo by reduced O2 metabolites, becoming potential endogenous tyrosine phosphatase inhibitors. Because of their potency, peroxides of vanadate may be useful as probes for the study of protein phosphotyrosine turnover.

Granulocytes↗
PubMed1994

Zinc, vanadate and selenate inhibit the tri-iodothyronine-induced expression of fatty acid synthase and malic enzyme in chick-embryo hepatocytes in culture.

Insulin regulates the expression of genes involved in a variety of metabolic processes. In chick-embryo hepatocytes in culture, insulin amplifies the tri-iodothyronine (T3)-induced enzyme activity, and the level and rate of transcription of mRNA for both fatty acid synthase (FAS) and malic enzyme (ME). Insulin alone, however, has little or no effect on the expression of these genes. In chick-embryo hepatocytes, the mechanism by which insulin regulates the expression of these or other genes is not known. Several recent studies have compared the effects of zinc, vanadate and selenate on insulin-sensitive processes in an attempt to probe the mechanism of insulin action. Because zinc, vanadate and selenate mimic the effects of insulin on several processes, they have been termed insulin-mimetics. We have studied the effect of zinc, vanadate and selenate on the T3-induced expression of both FAS and ME. Like insulin, these agents had little or no effect on the basal activities for FAS and ME in chick-embryo hepatocytes in culture for 48 h. Unlike insulin, however, zinc, vanadate and selenate inhibited the T3-induced activities and mRNA levels of both FAS and ME. Maximal inhibition was achieved at concentrations of 50 microM zinc or vanadate, or 20 microM selenate. Zinc and vanadate also inhibited the T3-induced transcription of the FAS and ME genes. Although the mechanism of this inhibition is unknown, our results indicate that it is not mediated through inhibition of binding of T3 to its nuclear receptor nor through a general toxic effect. Thus zinc, vanadate and selenate are not insulin-mimetics under all conditions, and their effects on other insulin-sensitive processes may be fortuitous and unrelated to actions or components of the insulin signalling pathway.

Animals↗
PubMed1996

Possible involvement of a tyrosine kinase-dependent pathway in the regulation of phosphoinositide metabolism by vanadate in normal mouse islets.

The potential roles of protein tyrosine kinases (TKs) and of phosphotyrosine phosphatases (PTPs) in pancreatic islet function are not known. In this study, we investigated whether vanadate, a potent PTP inhibitor, affects phosphoinositide (PI) metabolism by a TK-dependent pathway in isolated mouse islets. To avoid the confounding effects of changes in Ca2+ influx, all experiments were performed in the absence of Ca2+. In the presence of 15mM glucose, vanadate, acetylcholine (ACh) or [Arg]vasopressin (AVP) strongly stimulated InsP production. Vanadate also increased PtdInsP levels in membranes. The TK inhibitor genistein (not its inactive analogues genistin and daidzein) significantly reduced vanadate effects, but was without effect in the absence of stimulation or in the presence of ACh or AVP. Islet proteins resolved by SDS/PAGE were analysed by immunobloting with anti-phosphotyrosine antibody. Under control conditions, several phosphotyrosyl-proteins (PYPs) were present. Vanadate increased phosphotyrosine residues on several PYPs, notably two proteins of 145 and 85 kDa. This effect was prevented by genistein, p145 and p85 could correspond to phospholipate Cgamma(PLCgamma) and the regulatory subunit of PtdIns-3-kinase (PtdIns-3K) respectively. Both proteins are expressed in islets, as revealed by immunoblots with specific antibodies. Tungstate, another PTP inhibitor, reproduced vanadate effects, but inhibition of PtdIns-3K by wortmannin failed to affect vanadate-increased PtdInsP levels. Incubation of the islets in the presence of 10% (v/v) fetal calf serum instead of BSA increased InsP production and this effect was prevented by genistein. These results suggest that inhibition of PTP increases InsP production in mouse islets by a TK-dependent pathway. They also provide evidence for a potential role of TK and PTP in pancreatic B-cell function.

Acetylcholine↗
PubMedDate not supplied

Topical vanadate optimizes collagen organization within granulation tissue.

Systemic ingestion of vanadate, a nonspecific inhibitor of tyrosine phosphatases, doubles wound breaking strength, enhances the packing of collagen fibers, and prevents the appearance of myofibroblasts in granulation tissue. Will the local application of vanadate mimic the systemic effects? Pairs of polyvinyl alcohol sponges, each with a central reservoir and attached injection port, were subcutaneously implanted in rats. Daily, one implant received 0.2 ml of saline and the other received 0.2 ml of 0.03 mM vanadate in saline. On day 7, harvested sponges had equivalent wet weights. The vanadate-treated sponges had fibroblasts separated by connective tissue, with a more intense birefringence of the collagen fibers. Transmission electron microscopy showed collagen more uniformly packed in the vanadate treated sponges where collagen fibers were equally spaced and had equal diameters. By immunohistology, myofibroblasts, defined by the expression of alpha-smooth muscle actin within stress fibers, were absent in vanadate-treated granulation tissue. The expression of alpha-smooth muscle actin was restricted to smooth muscle cells of blood vessels. Controls had densely packed alpha-smooth muscle actin staining myofibroblasts, weak birefringence, and randomly spaced collagen fibers with irregular diameters. We conclude that the local application of vanadate prevents the appearance of myofibroblasts and optimizes the organization of collagen fibers in developing granulation tissue.

Administration, Topical↗
PubMed1995

P-glycoprotein is stably inhibited by vanadate-induced trapping of nucleotide at a single catalytic site.

P-glycoprotein (Pgp or multidrug-resistance protein) shows drug-stimulated ATPase activity. The catalytic sites are known to be of low affinity and specificity for nucleotides. From the sequence, two nucleotide sites are predicted per Pgp molecule. Using plasma membranes from a multidrug-resistant Chinese hamster ovary cell line, which are highly enriched in Pgp, we show that vanadate-induced trapping of nucleotide at a single catalytic site produces stably inhibited Pgp, with t 1/2 for reactivation of ATPase activity of 84 min at 37 degrees C and >30 h at 4 degrees C. Reactivation of ATPase correlated with release of trapped nucleotide. Concentrations of MgATP and MgADP required to produce 50% inhibition were 9 and 15 microM, respectively, thus the apparent affinity for nucleotide is greatly increased by vanadate-trapping. The trapped nucleotide species was ADP. Divalent Cation was required, with magnesium, manganese, and cobalt all effective: cobalt yielded a very stable inhibited species, t1/2 at 37 degrees C = 18 h. No photocleavage of Pgp was observed after vanadate trapping with MgATP, nor was UV-induced photolabeling of Pgp by trapped adenine nucleotide observed. Vanadate-trapping with 8-azido-ATP followed by UV irradiation caused permanent inactivation and specific labeling of Pgp. Vanadate-induced inhibition was also shown with pure, reconstituted Pgp, with similar characteristics to those in plasma membranes. Vanadate trapping overcomes technical difficulties posed by lack of high affinity nucleotide-binding site(s) or a covalent enzyme-phosphate catalytic intermediate in Pgp. The finding that vanadate trapping of nucleotide at just one site/Pgp is sufficient to give full inhibition at ATPase activity shows that the two predicted nucleotide sites can not function independently as catalytic sites.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and pervanadate.

Vanadate and pervanadate (the complexes of vanadate with hydrogen peroxide) are two commonly used general protein-tyrosine phosphatase (PTP) inhibitors. These compounds also have insulin-mimetic properties, an observation that has generated a great deal of interest and study. Since a careful kinetic study of the two inhibitors has been lacking, we sought to analyze their mechanisms of inhibition. Our results show that vanadate is a competitive inhibitor for the protein-tyrosine phosphatase PTP1B, with a Ki of 0.38+/-0.02 microM. EDTA, which is known to chelate vanadate, causes an immediate and complete reversal of the inhibition due to vanadate when added to an enzyme assay. Pervanadate, by contrast, inhibits by irreversibly oxidizing the catalytic cysteine of PTP1B, as determined by mass spectrometry. Reducing agents such as dithiothreitol that are used in PTP assays to keep the catalytic cysteine reduced and active were found to convert pervanadate rapidly to vanadate. Under certain conditions, slow time-dependent inactivation by vanadate was observed; since catalase blocked this inactivation, it was ascribed to in situ generation of hydrogen peroxide and subsequent formation of pervanadate. Implications for the use of these compounds as inhibitors and rationalization for some of their in vivo effects are considered.

Animals↗
PubMed1999

Interaction of vanadate with the cloned beta cell K(ATP) channel.

Vanadate is used as a tool to trap magnesium nucleotides in the catalytic site of ATPases. However, it has also been reported to activate ATP-sensitive potassium (K(ATP)) channels in the absence of nucleotides. K(ATP) channels comprise Kir6.2 and sulfonylurea receptor subunits (SUR1 in pancreatic beta cells, SUR2A in cardiac and skeletal muscle, and SUR2B in smooth muscle). We explored the effect of vanadate (2 mM), in the absence and presence of magnesium nucleotides, on different types of cloned K(ATP) channels expressed in Xenopus oocytes. Currents were recorded from inside-out patches. Vanadate inhibited Kir6.2/SUR1 currents by approximately 50% but rapidly activated Kir6.2/SUR2A ( approximately 4-fold) and Kir6. 2/SUR2B ( approximately 2-fold) currents. Mutations in SUR that abolish channel activation by magnesium nucleotides did not prevent the effects of vanadate. Studies with chimeric SUR indicate that the first six transmembrane domains account for the difference in both the kinetics and the vanadate response of Kir6.2/SUR1 and Kir6. 2/SUR2A. Boiling the vanadate solution, which removes the decavanadate polymers, largely abolished both stimulatory and inhibitory actions of vanadate. Our results demonstrate that decavanadate modulates K(ATP) channel activity via the SUR subunit, that this modulation varies with the type of SUR, that it differs from that produced by magnesium nucleotides, and that it involves transmembrane domains 1-6 of SUR.

Adenosine Triphosphate↗
PubMed2001

Vanadate facilitates interferon alpha-mediated apoptosis that is dependent on the Jak/Stat pathway.

Type I interferon (IFN)-dependent inhibition of cell growth can occur either in the absence or presence of apoptosis. The mechanisms that determine whether or not cells undergo apoptosis after exposure to IFN-alpha are not clear. This study shows that a variety of cell lines that display growth inhibition but not apoptosis in response to IFN-alpha will undergo programmed cell death when low concentrations of the protein-tyrosine phosphatase inhibitor vanadate are added with IFN-alpha. In contrast, the combination of tumor necrosis factor-alpha with vanadate did not trigger apoptosis in these cells. Caspase-3 activity was detected only in cells exposed to IFN-alpha and vanadate but not to IFN-alpha or vanadate alone. The ability of IFN-alpha and vanadate to induce apoptosis did not require expression of p53 and was blocked by N-acetyl-l-cysteine. Activation of the Jak/Stat pathway and expression of IFN-inducible genes was not altered by incubation of cells with IFN-alpha and vanadate compared with IFN-alpha alone. However, mutant cells lacking Stat1, Stat2, Jak1, or Tyk2, or cells expressing kinase inactive Jak1 or Tyk2 did not undergo apoptosis in the presence of IFN-alpha and vanadate. These results suggest that IFN-alpha stimulation of Stat-dependent genes is necessary, but not sufficient, for this cytokine to induce apoptosis. Another signaling cascade that involves the activity of a protein-tyrosine phosphatase and/or the generation of reactive oxygen species may play an important role in promoting IFN-alpha-induced apoptosis.

Acetylcysteine↗
PubMed2002

Vanadate-induced expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor through phosphatidylinositol 3-kinase/Akt pathway and reactive oxygen species.

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor composed of HIF-1 alpha and HIF-1 beta/aryl hydrocarbon nuclear translocator subunits. HIF-1 expression is induced by hypoxia, growth factors, and activation of oncogenes. In response to hypoxia, HIF-1 activates the expression of many genes including vascular endothelial growth factor (VEGF) and erythropoietin. HIF-1 and VEGF play an important role in angiogenesis and tumor progression. Vanadate is widely used in industry, and is a potent inducer of tumors in humans and animals. In this study, we demonstrate that vanadate induces HIF-1 activity through the expression of HIF-1alpha but not HIF-1 beta subunit, and increases VEGF expression in DU145 human prostate carcinoma cells. We also studied the signaling pathway involved in vanadate-induced HIF-1 alpha and VEGF expression and found that phosphatidylinositol 3-kinase/Akt signaling was required for HIF-1 and VEGF expression induced by vanadate, whereas mitogen-activated protein kinase pathway was not required. We also found that reactive oxygen species (ROS) were involved in vanadate-induced expression of HIF-1 and VEGF in DU145 cells. The major species of ROS responsible for the induction of HIF-1 and VEGF expression was H(2)O(2). These results suggest that the expression of HIF-1 and VEGF induced by vanadate through PI3K/Akt may be an important signaling pathway in the vanadate-induced carcinogenesis, and ROS may play an important role.

Antioxidants↗
PubMed1999

Interaction of the tyrosine phosphatase inhibitor ortho-vanadate on stimulus--secretion coupling in pancreatic acinar cells.

BACKGROUND: The effect of the tyrosine phosphatase inhibitor ortho-vanadate on stimulus-secretion coupling was investigated in isolated rat pancreatic acini. METHODS AND RESULTS: Ortho-vanadate (10(3)M) reduced cholecystokinin (CCK)-8 (10(10) M)-stimulated amylase release by 40% (IC50 = 5 x 10(4) M). In contrast, preincubation with 10(3) M ortho-vanadate increased secretin (5 x 10(9) M) and vasoactive intestinal peptide (VIP) (10(7) M)-induced amylase release by 65% and 80% (IC50= 3 x 10(-4) M), respectively. 8-Bromo-cyclic adenosine-5-monophosphate (cAMP) (10(-4) M) and phorbol ester (10(-5) M)-induced secretion was increased by 60% and 50%, respectively, whereas thapsigargin-induced amylase release was not affected. Ortho-vanadate did not affect CCK-8 binding or VIP-induced cAMP synthesis in isolated acini. In contrast, preincubation with 10(-4) M ortho-vanadate resulted in a significant reduction of CCK-8-induced intracellular calcium release. In streptolysin-O-permeabilized acini, ortho-vanadate reduced calcium-induced amlyase secretion by 50%. CONCLUSIONS: The present data provide indirect evidence of a differential involvement of protein tyrosine dephosphorylation in both cAMP- and IP3/Ca(2+)-mediated pancreatic secretion. The differential effects of ortho-vanadate on cAMP- versus calcium-mediated secretion correspond to the results obtained with receptor-independent intracellularly acting secretagogues. Further experiments must define the tyrosine phosphatases involved in both signal-transduction pathways.

Amylases↗
PubMed1998

Vanadate-sensitive microsomal ATPases and microsomal 45Ca2+ uptake in tracheal epithelial cells.

Cytosolic free Ca2+ plays important roles in the regulation of physiological processes in tracheal epithelial cells and is probably regulated by many ion-transporting ATPases in these cells. Therefore, the effect of vanadate was investigated to characterize microsomal ion-transporting ATPases. Dose response experiments showed that vanadate had a biphasic effect on the microsomal ATPase activity: a decrease at the vanadate concentration below 100 microM, and a steep decrease at the concentration above 100 microM. The dose response data were fitted to two sigmoidal functions, corresponding to a low-affinity vanadate-sensitive (LAVS) ATPase and a high-affinity vanadate-sensitive (HAVS) ATPase. In 45Ca2+ uptake experiments, both LAVS and HAVS ATPases mediated microsomal 45Ca2+ uptake. The LAVS ATPase was selectively sensitive to thapsigargin in both ATPase activity and 45Ca2+ uptake, suggesting that it is an ER/SR-type intracellular Ca2+-ATPase. Although the HAVS ATPase mediated one-fourth of microsomal 45Ca2+ uptake, its activity was not sensitive to thapsigargin. These results indicate that the activities of these two vanadate-sensitive ATPases are mediated by different enzymes, since thapsigargin only blocks the activity of LAVS ATPase. In conclusion, there are two types of vanadate-sensitive microsomal ATPases, and these ATPases mediate microsomal 45Ca2+ uptake in airway epithelial cells.

Adenosine Triphosphatases↗
PubMed1992

Vanadate stimulates D-glucose transport into sarcolemmal vesicles from rat skeletal muscles.

Vanadate is known to have various insulin-like actions including activation of D-glucose uptake into the skeletal muscle and adipose tissue. In this study, we examined the effect of orthovanadate on D-glucose uptake into sarcolemmal vesicles prepared from rat hind limb skeletal muscles. In the presence of 10 mM vanadate, the initial rate of D-glucose uptake into sarcolemmal vesicles was enhanced 4-5 times above the basal value. Half-maximal concentration for this effect of vanadate was 3 mM. The D-glucose uptake was also stimulated by metavanadate, but not by selenite, selenate, or molybdate. When vanadate was removed from the vesicles by dilution and centrifugation, D-glucose uptake into the vesicles returned to the basal level, indicating that the effect of vanadate was reversible. Saturation curves showed that the Vmax value for the D-glucose uptake was enhanced more than 4-fold by 10 mM vanadate. Therefore, the activation of D-glucose uptake was due, at least in part, to a large increase in the Vmax value. These results suggest that vanadate increases the intrinsic activity (turnover number) of skeletal muscle glucose transporters in a reversible manner.

Animals↗
PubMed2001

Vanadate ingestion increases the gain in wound breaking strength and leads to better organized collagen fibers in rats during healing.

Repair of incision wounds closed by suturing is evaluated by the progressive gain in wound breaking strength. Previously the closure of open wounds in rats ingesting vanadate, an inhibitor of tyrosine phosphate phosphatases, was shown to occur with deposition of more uniformly organized collagen fiber bundles. The hypothesis of this study was that deposition of more uniformly organized collagen fibers would enhance the gain in wound breaking strength of incisional wounds. Six adult rats received vanadate-supplemented saline drinking water for 1 week before placement of two 6-cm, parallel, suture-closed wounds on their backs. Six control rats received identical wounds and were given saline drinking water. The drinking water regimen was continued for 1 week after wounding, and then wound strength was tested with a tensiometer and tissue samples were obtained for histologic evaluation. Wound breaking strength doubled in vanadate-treated rats compared with controls. Bright-field and polarized light microscopy showed that the connective tissue matrix of granulation tissue from control rats was oriented perpendicular to the surface of the skin. In contrast, the connective tissue matrix of granulation tissue from vanadate-treated rats was oriented parallel to the skin surface. The gap in granulation tissue between the edges of the wounds in the vanadate-treated rats was greater than that in controls. Electron microscopy showed that wounds in the vanadate-treated contained uniform collagen fibers that were 20 percent greater in diameter and more evenly spaced than they were in controls. It is proposed that these changes in the organization of collagen fibers within incisional wounds were responsible for the increased wound breaking strength observed in rats ingesting vanadate.

Animals↗
PubMed1981

Reduction of Vanadate by ascorbic acid and noradrenaline in synaptosomes.

The effect of ascorbic acid and noradrenaline on the inhibition of synaptosomal membrane ATPase by vanadate has been studied. Ascorbic acid (2 x 10(-3) M) and noradrenaline (10(-4) M) partly reversed the inhibition by vanadate (10(-6) M); however, when both were administered together the inhibition was completely eliminated. Using electron spin resonance (ESR) spectroscopy, we detected that ascorbic acid (10(-3) M) caused a 42% of reduction of vanadate (10(-4) M). Noradrenaline (10(-4) M) alone also reduced vanadate (10(-4) M) partially. When ascorbic acid and noradrenaline were present together all the vanadate was reduced to vanadyl. The concentration of ascorbic acid present in the brain under physiological conditions is identical to that found effective in our experiments. We suggest that ascorbic acid may protect the ATPase, at least in part, from inhibition by vanadate as a consequence of reducing vanadate to vanadyl. In those tissues where noradrenaline is also present a complete reduction of endogenous vanadium can be presumed.

Animals↗