Actin as a potential target for decavanadate

Ramos, Susana; Moura, José J. G.; Aureliano, Manuel

doi:10.1016/j.jinorgbio.2010.08.001

Cited by 20 publications

(33 citation statements)

References 45 publications

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“…In fact, decavanadate interaction with both G-and F-actin results in a concomitant vanadate reduction to vanadyl (V(IV)). 13,14 Typical EPR vanadium(IV) signals can be detected upon decavanadate incubation with actin, whereas the presence of ATP in the medium, once again, prevents decavanadate reduction to vanadyl, as described above and reported previously. 13,14 But once vanadate is reduced to vanadyl, does the reduced form of vanadium bind to actin?…”

Section: Introductionsupporting

confidence: 70%

“…It is believed that one of the main targets of vanadium in the cell will be actin, regulating or preventing many events. 13,14 Therefore, it will be of extreme importance to clarify the mode of interaction and the effects of vanadium on actin structure and function. In the present report, a combination of kinetic studies and 51 V NMR, EPR, fluorescence and UV/Vis spectroscopy techniques was used to establish the interaction and/or effects of vanadyl, vanadate and decavanadate on actin structure and function.…”

Section: Introductionmentioning

confidence: 99%

“…The lack of quenching of F-actin intrinsic fluorescence by vanadyl suggests that the tryptophans present in the protein are protected from vanadium effects when the actin is present in its polymerized form. 14,30 Eventually, actin conformational changes induced during actin polymerization prevent the vanadium quenching. However, for higher vanadyl concentrations from 200 to 500 mM, a maximum of 75% intrinsic protein quenching was observed, as described elsewhere.…”

Section: Introductionmentioning

confidence: 99%

“…14,30 However, many biochemical studies using vanadium complexes and, particularly, decavanadate (with absorptions at 360 and 400 nm 7,31 ), do not take into consideration those effects, which decreases the fluorescence measurements accuracy. For the maximum decavanadate concentration referred to in these studies, 20 mM, (meaning 0.2 mM total vanadium), the absorbance values at excitation and emission wavelengths used in assays (295 and 340 nm, respectively) attain to a sum of 0.841 O.D.…”

Section: Introductionmentioning

confidence: 99%

“…14,30 Since it is known that the larger the value of the ATP exchange rate, the more available the cleft should be, 38 it can be concluded that vanadyl and decavanadate are clearly promoting structural alterations on actin ATP binding sites.…”

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confidence: 99%

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Recent advances into vanadyl, vanadate and decavanadate interactions with actin

2012

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Although the number of papers about ''vanadium'' has doubled in the last decade, the studies about ''vanadium and actin'' are scarce. In the present review, the effects of vanadyl, vanadate and decavanadate on actin structure and function are compared. Decavanadate 51 V NMR signals, at À516 ppm, broadened and decreased in intensity upon actin titration, whereas no effects were observed for vanadate monomers, at À560 ppm. Decavanadate is the only species inducing actin cysteine oxidation and vanadyl formation, both processes being prevented by the natural ligand of the protein, ATP. Vanadyl titration with monomeric actin (G-actin), analysed by EPR spectroscopy, reveals a 1 : 1 binding stoichiometry and a K d of 7.5 mM À1 . Both decavanadate and vanadyl inhibited G-actin polymerization into actin filaments (F-actin), with a IC 50 of 68 and 300 mM, respectively, as analysed by light scattering assays, whereas no effects were detected for vanadate up to 2 mM. However, only vanadyl (up to 200 mM) induces 100% of G-actin intrinsic fluorescence quenching, whereas decavanadate shows an opposite effect, which suggests the presence of vanadyl high affinity actin binding sites. Decavanadate increases (2.6-fold) the actin hydrophobic surface, evaluated using the ANSA probe, whereas vanadyl decreases it (15%). Both vanadium species increased the e-ATP exchange rate (k = 6.5 Â 10 À3 s À1 and 4.47 Â 10 À3 s À1 for decavanadate and vanadyl, respectively). Finally, 1 H NMR spectra of G-actin treated with 0.1 mM decavanadate clearly indicate that major alterations occur in protein structure, which are much less visible in the presence of ATP, confirming the preventive effect of the nucleotide on the decavanadate interaction with the protein. Putting it all together, it is suggested that actin, which is involved in many cellular processes, might be a potential target not only for decavanadate but above all for vanadyl. By affecting actin structure and function, vanadium can regulate many cellular processes of great physiological significance.

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Section: Introductionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Recent advances into vanadyl, vanadate and decavanadate interactions with actin

2012

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Im Kampf gegen Krebs: Polyoxometallate als nächste Generation metallhaltiger Medikamente

2018

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Polyoxometallate (POMs) haben großes Potenzial, verschiedene Tumorarten zu inhibieren; ihre Toxizität und unspezifischen Wechselwirkungen mit Biomolekülen verhindern jedoch eine klinische Anwendung. Der Schwerpunkt bei biologisch aktiven POMs liegt gegenwärtig auf organisch funktionalisierten POMs und POM‐basierten Nanokomposit‐Strukturen, da diese Hybride eine erhöhte Aktivität gegen Tumoren aufweisen, bei einer gleichzeitig deutlich verringerten Toxizität gegen normale Zellen. Während die Antitumoraktivität von POMs ausreichend beschrieben ist, sind ihre Wirkungsmechanismen noch weitgehend unbekannt. Dieser Aufsatz gibt einen Überblick über die zytotoxischen Effekte von POMs, wobei der Schwerpunkt auf POM‐basierten Hybriden und Nanokomposit‐Strukturen liegen soll. Postulierte Wirkungsmechanismen werden vorgestellt und molekulare Targets identifiziert. POMs könnten sich zur nächsten Generation metallhaltiger Krebsmedikamente entwickeln, die selektiv nur Krebszellen angreifen und gesunde Zellen verschonen.

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Inhibition of Mitochondrial ATP Synthesis and Regulation of Oxidative Stress Based on {SbW₈O₃₀} Determined by Single‐Cell Proteomics Analysis

et al. 2021

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The 10-nuclear heteroatom cluster modified {SbW 8 O 30 }w as successfully synthesized and exhibited inhibitory activity (IC 50 = 0.29 mM). Based on proteomics analysis, Na 4 Ni 2 Sb 2 W 2-SbW 8 inhibited ATPproduction by affecting the expression of 16 related proteins,h indering metabolic functions in vivo and cell proliferation due to reactive oxygen species (ROS) stress.Inparticular,the lowexpression of FAD/ FMN-binding redox enzymes (relative expression ratio of the experimental group to the control = 0.43843) could be attributed to the redoxmechanism of Na 4 Ni 2 Sb 2 W 2-SbW 8 ,which was consistent with the effect of polyoxometalates (POMs) and FMN-binding proteins on ATPformation. An electrochemical study showed that Na 4 Ni 2 Sb 2 W 2-SbW 8 combined with FMN to form Na 4 Ni 2 Sb 2 W 2-SbW 8-2FMN complex through ao ne-electron process of the Wa toms.N a 4 Ni 2 Sb 2 W 2-SbW 8 acted as catalase and glutathione peroxidase to protect the cell from ROSstress,and the inhibition rates were 63.3 %at1.77 mMof NADPH and 86.06 %a t1 0.62 mMo f2-hydroxyterephthalic acid. Overall, our results showed that POMs can be specific oxidative/antioxidant regulatory agents.

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Actin as a potential target for decavanadate

Cited by 20 publications

References 45 publications

Recent advances into vanadyl, vanadate and decavanadate interactions with actin

Recent advances into vanadyl, vanadate and decavanadate interactions with actin

Im Kampf gegen Krebs: Polyoxometallate als nächste Generation metallhaltiger Medikamente

Inhibition of Mitochondrial ATP Synthesis and Regulation of Oxidative Stress Based on {SbW₈O₃₀} Determined by Single‐Cell Proteomics Analysis

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Actin as a potential target for decavanadate

Cited by 20 publications

References 45 publications

Recent advances into vanadyl, vanadate and decavanadate interactions with actin

Recent advances into vanadyl, vanadate and decavanadate interactions with actin

Im Kampf gegen Krebs: Polyoxometallate als nächste Generation metallhaltiger Medikamente

Inhibition of Mitochondrial ATP Synthesis and Regulation of Oxidative Stress Based on {SbW8O30} Determined by Single‐Cell Proteomics Analysis

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Product

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Inhibition of Mitochondrial ATP Synthesis and Regulation of Oxidative Stress Based on {SbW₈O₃₀} Determined by Single‐Cell Proteomics Analysis