Interactions of vanadate oligomers with sarcoplasmic reticulum Ca2+-ATPase

Aureliano, Manuel; Madeira, Vı́tor M.C.

doi:10.1016/0167-4889(94)90249-6

Cited by 50 publications

(99 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Time course of G-actin (8 lM) polymerization (in Tris 2 mM, CaCl 2 0.2 mM, ATP 10 lM, pH 7.5), monitored by light-scattering at 546 nm, 25°C, in the absence (a) and in the presence of 4 mM (b) and 8 mM (c) of decavanadate (total vanadate concentration) added to the buffer just before starting the polymerization (with KCl 100 mM, MgCl 2 2 mM) at 25°C. spectroscopy [17,36]. Only for metavanadate concentrations at the micromolar range, orthovanadate species are exclusively present [14].…”

Section: Nmr Characterization Of Metavanadate and Decavanadate Solutionsmentioning

confidence: 99%

Decavanadate interactions with actin: Inhibition of G-actin polymerization and stabilization of decameric vanadate

Ramos

Manuel

Tiago

et al. 2006

Journal of Inorganic Biochemistry

Self Cite

101

View full text Add to dashboard Cite

Decameric vanadate species (V10) inhibit the rate and the extent of G-actin polymerization with an IC50 of 68 ± 22 lM and 17 ± 2 lM, respectively, whilst they induce F-actin depolymerization at a lower extent. On contrary, no effect on actin polymerization and depolymerization was detected for 2 mM concentration of ''metavanadate'' solution that contains ortho and metavanadate species, as observed by combining kinetic with 51 V NMR spectroscopy studies. Although at 25°C, decameric vanadate (10 lM) is unstable in the assay medium, and decomposes following a first-order kinetic, in the presence of G-actin (up to 8 lM), the half-life increases 5-fold (from 5 to 27 h). However, the addition of ATP (0.2 mM) in the medium not only prevents the inhibition of G-actin polymerization by V10 but it also decreases the half-life of decomposition of decameric vanadate species from 27 to 10 h. Decameric vanadate is also stabilized by the sarcoplasmic reticulum vesicles, which raise the half-life time from 5 to 18 h whereas no effects were observed in the presence of phosphatidylcholine liposomes, myosin or G-actin alone. It is proposed that the ''decavanadate'' interaction with G-actin, favored by the G-actin polymerization, stabilizes decameric vanadate species and induces inhibition of G-actin polymerization. Decameric vanadate stabilization by cytoskeletal and transmembrane proteins can account, at least in part, for decavanadate toxicity reported in the evaluation of vanadium (V) effects in biological systems.

show abstract

Section: Nmr Characterization Of Metavanadate and Decavanadate Solutionsmentioning

confidence: 99%

Decavanadate interactions with actin: Inhibition of G-actin polymerization and stabilization of decameric vanadate

Ramos

Manuel

Tiago

et al. 2006

Journal of Inorganic Biochemistry

Self Cite

101

View full text Add to dashboard Cite

show abstract

“…Spectra of 2 mM vanadium(V)-citrate complex solutions were also obtained in the same reaction medium, in the absence and presence of 2.5 mg/ml of SR preparations. The spectra were acquired at room temperature, spectral with 40,355 Hz, accumulation time 0.05 s, number of transients between 12,000 and 25,000 and relaxation delay 0.01 s. For quantitative measurements all of the spectral parameters were kept constant [12].…”

Section: Nmr Measurementsmentioning

confidence: 99%

“…Moreover, the use of vanadate is related to the catalytic site of Ca 2+ ATPase, which contains an aspartyl that is phosphorylated during the catalytic cycle thereby forming an acyl phosphate anhydride [11]. In addition to monomeric vanadate species, it has been reported that other vanadate oligomers interact with the SR calcium pump [12]. It has been demonstrated that some of the interactions, e.g.…”

Section: Introductionmentioning

confidence: 99%

Interactions of vanadium(V)–citrate complexes with the sarcoplasmic reticulum calcium pump

Aureliano

Tiago

Gândara

et al. 2005

Journal of Inorganic Biochemistry

Self Cite

View full text Add to dashboard Cite

Among the biotargets interacting with vanadium is the calcium pump from the sarcoplasmic reticulum (SR). To this end, initial research efforts were launched with two vanadium(V)-citrate complexes, namely (NH 4 51 V NMR spectroscopy. Upon dissolution in the reaction medium (concentration range: 4-0.5 mM), both vanadium(V):citrate (VC) and peroxovanadium(V):citrate (PVC) complexes are partially converted into vanadate oligomers. A 1 mM solution of the PVC complex, containing 184 lM of the PVC complex, 94 lM oxoperoxovanadium(V) (PV) species, 222 lM monomeric (V1), 43 lM dimeric (V2) and 53 lM tetrameric (V4) species, inhibits Ca 2+ accumulation by 75 %, whereas a solution of the VC complex of the same vanadium concentration, containing 98 lM of the VC complex, 263 lM monomeric (V1), 64 lM dimeric (V2) and 92 lM tetrameric (V4) species inhibits the calcium pump activity by 33 %. In contrast, a 1 mM metavanadate solution, containing 460 lM monomeric (V1), 90.2 lM dimeric (V2) and 80 lM tetrameric (V4) species, has no effect on Ca 2+ accumulation. The NMR signals from the VC complex (À548.0 ppm), PVC complex (À551.5 ppm) and PV (À611.1 ppm) are broadened upon SR vesicle addition (2.5 mg/ml total protein). The relative order for the half width line broadening of the NMR signals, which reflect the interaction with the protein, was found to be V4 > PVC > VC > PV > V2 = V1 = 1, with no effect observed for the V1 and V2 signals. Putting it all together the effects of two vanadium(V)-citrate complexes on the modulation of calcium accumulation and ATP hydrolysis by the SR calcium pump reflected the observed variable reactivity into the nature of key species forming upon dissolution of the title complexes in the reaction media.

show abstract

“…Although decavanadate interacts most strongly with the E2 conformation of the Ca 2+ -ATPase, as do some of the other drugs described above, decavanadate also interacts with other conformations. 6,8 Therefore, decavanadate exhibits a particular feature that may be useful for the understanding of the mode of action of ion pump inhibitors in general. Besides, the specific behaviour of decavanadate towards ion pumps may guide the development of new drugs that would have these pumps as therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 Therefore, the vanadate mode of action may involve formation of an E2V analogue after condensation of vanadate to the enzyme phosphorylation site, at aspartate residue 351. Analysis of the E2 conformation clearly shows structural changes relative to conformation E1 (Fig.…”

Section: Introductionmentioning

confidence: 99%

Ion pumps as biological targets for decavanadate

2013

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Interactions of vanadate oligomers with sarcoplasmic reticulum Ca2+-ATPase

Cited by 50 publications

References 39 publications

Decavanadate interactions with actin: Inhibition of G-actin polymerization and stabilization of decameric vanadate

Decavanadate interactions with actin: Inhibition of G-actin polymerization and stabilization of decameric vanadate

Interactions of vanadium(V)–citrate complexes with the sarcoplasmic reticulum calcium pump

Ion pumps as biological targets for decavanadate

Contact Info

Product

Resources

About