Inhibitory effects of decavanadate on several enzymes and Leishmania tarentolae In Vitro

Turner, Tracy A.; Nguyen, V. H.; McLauchlan, Craig C.; Dymon, Zaneta; Dorsey, Benjamin M.; Hooker, Jaqueline D.; Jones, Marjorie A.

doi:10.1016/j.jinorgbio.2011.09.009

Cited by 78 publications

(75 citation statements)

References 94 publications

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“…These complexes are important to the biodistribution of the metal 3, 7, 12–18 For example, V is well known to complex with transferrin 1, 19, 20 thereby decreasing the potentially biologically active V pool in the blood 21–24 . However, transferrin is not the only enzyme that interacts with vanadium, and in particular the mode of action of vanadium compounds have been implicated in the inhibition of a range of different enzymes 1, 25–27 . It is well recognized that vanadium undergoes redox chemistry after administration 19 , and a wide range of hydrolytic coordination chemistry takes place forming complexes with both metabolites and proteins 7, 8, 11, 12, 19, 26, 28–35 .…”

Section: Introductionmentioning

confidence: 99%

Coordination chemistry may explain pharmacokinetics and clinical response of vanadyl sulfate in type 2 diabetic patients

et al. 2013

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Vanadium, abbreviated V, is an early transition metal that readily forms coordination complexes with a variety of biological products such as proteins, metabolites, membranes and other structures. The formation of coordination complexes stabilizes metal ions, which in turn impacts the biodistribution of the metal. To understand the biodistribution of V, V in oxidation state IV in the form of vanadyl sulfate (25, 50, 100 mg V daily) was given orally for 6 weeks to 16 persons with type 2 diabetes. Elemental V was determined using Graphite Furnas Atomic Absorption Spectrometry against known concentrations of V in serum, blood or urine. Peak serum V levels were 15.4±6.5, 81.7±40 and 319±268 ng/ml respectively, and mean peak serum V was positively correlated with dose administered (r=0.992, p=0.079), although large inter-individual variability was found. Total serum V concentration distribution fit a one compartment open model with a first order rate constant for excretion with mean half times of 4.7±1.6 days and 4.6±2.5 days for the 50 and 100 mg V dose groups respectively. At steady state, 24 hour urinary V output was 0.18±0.24 and 0.97±0.84 mg in the 50 and 100 mg V groups respectively, consistent with absorption of 1 percent or less of the administered dose. Peak V in blood and serum were positively correlated (r=0.971, p<0.0005). The serum to blood V ratio for the patients receiving 100 mg V was 1.7±0.45. Regression analysis showed that glycohemoglobin was a negative predictor of the natural log (ln) peak serum V (R2=0.40, p=0.009) and a positive predictor of the euglycemic hyperinsulinemic clamp results at high insulin values (R2=0.39, p=0.010). Insulin sensitivity measured by euglycemic hyperinsulinemic clamp was not significantly correlated with ln peak serum V. Globulin and glycohemoglobin levels taken together were negative predictors of fasting blood glucose (R2=0.49, p=0.013). Although V accumulation in serum was dose-dependent, no correlation between total serum V concentation and the insulin-like response was found in this first attempt to correlate anti-diabetic activity with total serum V. This study suggests that V pools other than total serum V are likely related to the insulin-like effect of this metal. These results, obtained in diabetic patients, document the need for consideration of the coordination chemistry of metabolites and proteins with vanadium in anti-diabetic vanadium complexes.

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Section: Introductionmentioning

confidence: 99%

Coordination chemistry may explain pharmacokinetics and clinical response of vanadyl sulfate in type 2 diabetic patients

et al. 2013

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“…51 Due to the ability of V 10 to interfere with several biological processes, such as calcium homeostasis, muscle contraction and oxidative stress, 8,54,55 not only in vitro but also in vivo, 52,53 decavanadate has recently been associated with the treatment of Leishmaniosis. 56 In this and probably in many other cases the mechanism of action of decavanadate progresses via the inhibition of the E1-E2 Ca 2+ -ATPases. However, mitochondria may be an additional target as several mitochondrial processes have been shown to be affected by decavanadate at nanomolar concentrations.…”

Section: Ca 2+ -Atpase Inhibitorsmentioning

confidence: 99%

Ion pumps as biological targets for decavanadate

2013

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The putative applications of poly-, oligo-and mono-oxometalates in biochemistry, biology, pharmacology and medicine are rapidly attracting interest. In particular, these compounds may act as potent ion pump inhibitors and have the potential to play a role in the treatment of e.g. ulcers, cancer and ischemic heart disease. However, the mechanism of action is not completely understood in most cases, and even remains largely unknown in other cases. In the present review we discuss the most recent insights into the interaction between mono-and polyoxometalate ions with ion pumps, with particular focus on the interaction of decavanadate with Ca 2+ -ATPase. We also compare the proposed mode of action with those of established ion pump inhibitors which are currently in therapeutic use. Of the 18 classes of compounds which are known to act as ion pump inhibitors, the complete mechanism of inhibition is only known for a handful. It has, however, been established that most ion pump inhibitors bind mainly to the E2 ion pump conformation within the membrane domain from the extracellular side and block the cation release. Polyoxometalates such as decavanadate, in contrast, interact with Ca 2+ -ATPase near the nucleotide binding site domain or at a pocket involving several cytoplasmic domains, and therefore need to cross through the membrane bilayer.In contrast to monomeric vanadate, which only binds to the E2 conformation, decavanadate binds to all protein conformations, i.e. E1, E1P, E2 and E2P. Moreover, the specific interaction of decavanadate with sarcoplasmic reticulum Ca 2+ -ATPase has been shown to be non-competitive with respect to ATP and induces protein cysteine oxidation with concomitant vanadium reduction which might explain the high inhibitory capacity of V 10 (IC 50 = 15 μM) which is quite similar to the majority of the established therapeutic drugs.

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“…On this ground, the decavanadate solution was suggested to be prepared by acidifying and then re-neutralizing the metavanadate solution subsequently before adding to the buffered culture media. However, there are still V 2 , V 4 , and V 5 present in this process (Iannuzzi et al 2006;Turner et al 2011). A kinetic study by means of UV-visible spectroscopy showed that the decomposition of V 10 at 25 C in the saline solution fits to a first-order kinetic process, with half-life of 16 h (Soares et al 2007b).…”

Section: Self-condensation Reactions Of Vanadatementioning

confidence: 99%

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

Wang

2013

Biomedical Inorganic Polymers

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Vanadate is widely used as an inhibitor of protein tyrosine phosphatases (PTPase) and is routinely applied in cell lysis buffers or immunoprecipitations of phosphotyrosyl proteins. Additionally, vanadate has been extensively studied for its antidiabetic and anticancer effects. In most studies, orthovanadate or metavanadate was used as the starting compound, whereas these "vanadate" solutions may contain more or less oligomerized species. Whether and how different species of vanadium compounds formed in the biological media exert specific biological effect is still a mystery. In the present commentary, we focus on the chemical, biochemical, and biological behaviors of vanadate. On the basis of species formation of vanadate in chemical and biological systems, we compared the biological effects and working mechanism of monovanadate with that of its oligomers, especially the decamer. We propose that different oligomers may exert a specific biological effect, which depends on their structures and the context of the cell types, by different modes of action.

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Inhibitory effects of decavanadate on several enzymes and Leishmania tarentolae In Vitro

Cited by 78 publications

References 94 publications

Coordination chemistry may explain pharmacokinetics and clinical response of vanadyl sulfate in type 2 diabetic patients

Coordination chemistry may explain pharmacokinetics and clinical response of vanadyl sulfate in type 2 diabetic patients

Ion pumps as biological targets for decavanadate

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

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