Disease relevance of Vanadate

• Vanadate normalizes hyperglycemia in two mouse models of non-insulin-dependent diabetes mellitus [1].
• Oral administration of vanadate (0.25 mg/ml in the drinking water) to ob/ob mice for 3 wk lowered blood glucose level from 236 +/- 4 to 143 +/- 2 mg/dl without effect on body weight [1].
• The metalion vanadate has insulin-like effects and has been advocated for use in humans as a therapeutic modality for diabetes mellitus [2].
• Lactate production during ischemia, an indication of anaerobic glycolysis, was significantly higher in hearts from vanadate-treated animals [3].
• The amino acids involved in transition-state stabilization for cysteinylphosphate hydrolysis were confirmed by the x-ray structure of the Yersinia PTPase complexed with vanadate, a transition-state mimic that binds covalently to the active-site cysteine [4].

Psychiatry related information on Vanadate

• Reduction of vanadate, a possible explanation of the effect of phenothiazines in manic-depressive psychosis [5].
• Much less inactivation occurs during turnover at long reaction times at higher pH (> pH 6), and the inactivation can be fully reversed by subsequent addition of vanadate [6].
• Inhibition by vanadate of the K+-dependent p-nitrophenylphosphatase activity catalyzed by the (Na+ + K+)-ATPase partially purified from pig kidney showed competitive behavior with the substrate, K+ and Mg2+ acted as cofactors in promoting that inhibition [7].

High impact information on Vanadate

• However, after nucleotide hydrolysis is inhibited by vanadate, unidirectional translocation ceases, and microtubules instead undergo irregular back-and-forth motion along their longitudinal axes [8].
• Inactivation of cytoplasmic dynein in the high-speed cytosol by vanadate-mediated UV photocleavage inhibited minus end-directed organelle motility by over 90% [9].
• Spindle elongation and the pattern of tubulin incorporation into the midzone, but not the poles, are ATP-dependent and vanadate-sensitive [10].
• As this protein shares several properties with the granule vanadate-sensitive ATPase II, we infer that this ATPase, of relative molecular mass 115,000, is the protein responsible for aminophospholipid translocation [11].
• It binds to microtubules under conditions of ATP depletion, possesses an ATPase activity and is sensitive to ultraviolet-induced, vanadate-dependent cleavage [12].

Chemical compound and disease context of Vanadate

• Here we examined whether acute and chronic administration of benzylamine and vanadate in vivo enhances glucose tolerance and reduces hyperglycemia in diabetic rats [13].
• Both actions are blocked by pertussis toxin and by the phosphotyrosine phosphatase inhibitor, vanadate [14].
• In FTO-2B hepatoma cells infected with retrovirus, vanadate rapidly (within 1 h) inhibited transcription of the PEPCK-neo gene and blocked induction of gene expression caused by the addition of either Bt2cAMP or dexamethasone to the cells [15].
• Glucose-6-phosphate transport investigated by light-scattering technique resulted in similar traces in control and vanadate-treated rat microsomes as well as in microsomes from human patients with glycogen storage disease type 1a [16].
• MKP-4 produced in Escherichia coli catalyzes vanadate-sensitive breakdown of p-nitrophenyl phosphate as well as in vitro inactivation of purified ERK2 [17].

Biological context of Vanadate

• Here we report similar photolabelling experiments with smooth muscle myosin (chicken gizzard) in which 3H-NANDP is trapped at the active site with vanadate and which show that both the heavy chains and the essential light chains are labelled [18].
• Positive inotropism of vanadate in cat papillary muscle [19].
• Vanadate-stimulated natriuresis [20].
• Nevertheless, ATP depletion or vanadate treatment of high [Ca2+]i fibres causes an approximately 50-fold increase of Ca2+ efflux into Ca2+-containing lithium seawater [21].
• Ventral photoreceptors may contain a guanyl nucleotide binding protein whose activation by vanadate or GTP-gamma-S induces the discrete waves [22].

Anatomical context of Vanadate

• Importance of cardiac cell membranes in vanadate-induced NADH oxidation [23].
• Negative and positive inotropic action of vanadate on atrial and ventricular myocardium [24].
• Glycogen synthase activity was reduced in skeletal muscle of diabetic rats (P less than 0.05) compared with controls and was increased to supranormal levels by vanadate treatment (P less than 0.01) [25].
• Although vanadate exerts beneficial insulin-like effects and potentiates the effect of insulin in sensitive tissue, it may result in undesirable activation of other target cells, such as mesangial cells [2].
• Failure of lithium to counteract vanadate-induced inhibition of red blood cell membrane Na+, K+-ATPase [26].

Associations of Vanadate with other chemical compounds

• Excitation of Limulus photoreceptors by vanadate and by a hydrolysis-resistant analog of guanosine triphosphate [22].
• The injection of vanadate or the hydrolysis-resistant analog of guanosine triphosphate, GTP-gamma-S, into ventral photoreceptors induces the production of discrete waves in the dark [22].
• To characterize the in vivo mechanism of action of vanadate, we examined meal tolerance, insulin-mediated glucose disposal, in vivo liver and muscle glycogen synthesis, and in vitro glycogen synthase activity in 90% partially pancreatectomized rats [25].
• However, EGF-R autophosphorylation increased significantly in plastic-adherent GEC that were stimulated with EGF at 4 degrees C or in the presence of vanadate, an inhibitor of phosphotyrosine phosphatases [27].
• Dicyclohexylcarbodiimide, which inhibits all proton pumps, and N-ethylmaleimide, which inhibits the proton pump of endocytic vesicles and lysosomes, but not mitochondria, prevented this adenosine triphosphate-dependent reappearance of acridine orange fluorescence, whereas vanadate did not [28].

Gene context of Vanadate

• No lag phase was detected between the time when cyclin A was added and the time when H1 histone kinase activity was produced in frog extracts, even in the presence of 2 mM vanadate, which blocks cdc25 activity [29].
• These results, together with the fact that vanadate-sensitive phosphatase activity was higher in confluent cells, suggest that phosphatases play a role in the down-regulation of p42/p44 MAPK activity [30].
• Importantly, culture of MO7E cells with vanadate (up to 10 mumol/L) resulted in a dose-dependent increase in GM-CSF-or IL-3-induced proliferation of up to 1.8-fold [31].
• One of these, an approximately 62-kDa protein, also associated with CSK in NIH 3T3 cells treated with vanadate prior to lysis and in NIH 3T3 cells expressing an activated c-Src mutant [32].
• We examined vanadate-induced nucleotide trapping in MRP1 stably expressed in KB cell membrane by using 8-azido-[alpha-(32)P]ATP [33].

Analytical, diagnostic and therapeutic context of Vanadate

• Stimulation of Na+/H+ exchange by epidermal growth factor (EGF) and serum as well as by vanadate ions is strongly inhibited after treatment of cells with nanomolar concentrations of PMA [34].
• With the rapid-freeze, deep-etch replica technique, the structural conformations of outer dynein arms in demembranated cilia from Tetrahymena were analyzed under two different conditions, i.e., in the absence of ATP and in the presence of ATP and vanadate [35].
• Freeze-fracture studies and negative staining of microsomal fractions treated with vanadate indicate that most of the membrane system of heater cells has a high Ca2+-ATPase density and is equivalent to skeletal muscle sarcoplasmic reticulum (SR) [36].
• Inhibitors of H+-ATPase (erythrosin B, diethyl stilbestrol, and vanadate) were found to alkalinize the growth medium of L. peruvianum cell cultures and to induce wound response genes in whole tomato plants [37].
• Active site of RNase: neutron diffraction study of a complex with uridine vanadate, a transition-state analog [38].

References