Browsing by Author "Aureliano, M."
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- Actin as a potential target for decavanadatePublication . Ramos, Susana; Moura, José J. G.; Aureliano, M.ATP prevents G-actin cysteine oxidation and vanadyl formation specifically induced by decavanadate, suggesting that the oxometalate–protein interaction is affected by the nucleotide. The ATP exchange rate is increased by 2-fold due to the presence of decavanadate when compared with control actin (3.1×10−3 s−1), and an apparent dissociation constant (kdapp) of 227.4±25.7 μM and 112.3±8.7 μM was obtained in absence or presence of 20 μM V10, respectively. Moreover, concentrations as low as 50 μM of decameric vanadate species (V10) increases the relative G-actin intrinsic fluorescence intensity by approximately 80% whereas for a 10-fold concentration of monomeric vanadate (V1) no effects were observed. Upon decavanadate titration, it was observed a linear increase in G-actin hydrophobic surface (2.6-fold), while no changes were detected for V1 (0–200 μM). Taken together, three major ideas arise: i) ATP prevents decavanadate-induced G-actin cysteine oxidation and vanadate reduction; ii) decavanadate promotes actin conformational changes resulting on its inactivation, iii) decavanadate has an effect on actin ATP binding site. Once it is demonstrated that actin is a new potential target for decavanadate, being the ATP binding site a suitable site for decavanadate binding, it is proposed that some of the biological effects of vanadate can be, at least in part, explained by decavanadate interactions with actin.
- Actomyosin modulation by peroxynitritePublication . Tiago, Teresa; Silva, D.; Santos, Ana; Aureliano, M.; Gutiérrez-Merino, CarlosIn the present work we address the oxidative modifications accounting for the structural and functional impairment of the actomyosin complex under the oxidative stress mediated by peroxynitrite (ONOO-). Experiments on purified myosin and actin have shown that submicromolar ONOO- concentrations produce strong inhibition of the F-actin stimulated myosin ATPase activity. The peroxynitrite-induced actomyosin impairment correlated with structural modifications that decrease the thermal stability of both actin and myosin leading to partially unfolded states. The results suggest a major role for the highly reactive cysteines on actin and on myosin and also for some critical methionines on G-actin. 3-nitrotyrosine does not contribute significantly to the observed functional alterations.
- Acute effects of vanadate oligomers on heart, kidney, and liver histology in the lusitanian toadfish (Halobatrachus didactylus)Publication . Aureliano, M.The contribution of vanadate oligomers to the acute histological effects of vanadium was analyzed in the heart, kidney, and liver of Halobatrachus didactylus (Schneider, 1801).A sublethal vanadium dose(5mM,1mL/kg)in the form of metavanadate(containing ortho and metameric species)or in the form of decavanadate (containing only decameric species) was intraperitoneally administered by injection, and specimens of H. didactylus were sacrificed at one and seven days postinjection. Sections of heart ventricle and renal and hepatic tissue were stained with hematoxylin-eosin and examined by light microscopy to identify vanadium-induced tissue injury. In addition, PicroSirius-stained ventricular sections were analyzed by bipolarized light microscopy to determine the fraction of myocardium occupied by the ventricular wall structural elements (collagen I, collagen III, and cardiac muscle). Both vanadate solutions produced similar effects in the renal tissue. Morphological alterations included damaged renal tubules showing disorganized epithelial cells in different states of necrosis. Reabsorbed renal tubules and hyperchromatic interstitial tissue were also observed. The hepatic tissue presented hyperchromatic and hypertrophied nuclei, along with necrotic and hypertrophied hepatocytes, and more severe changes were observed in the liver with exposure to decavanadate. Vanadate oligomers promoted evident tissue lesions in the kidney and liver, but not in the cardiac tissue. However, cardiac tissue structural changes were produced. For example, decavanadate induced a hypertrophy of the ventricle due to a decrease in the percentage of myocardium occupied by collagen fibers. In general, decavanadate was shown to be more toxic than metavanadate.
- An EXAFS approach to the study of polyoxometalate–proteiniInteractions: the case of decavanadate–actinPublication . Marques, M. P. M.; Gianolio, Diego; Ramos, Susana; Carvalho, Luís E. A. B.; Aureliano, M.Decavanadate−actin interactions were studied by EXAFS and XANES, allowing us to simultaneously probe, for the first time, all vanadium species in the system. V10 interacts with G-actin (at its ATP binding site), a V−SCys coordination having been verified along with oxidovanadium formation. V10’s interplay with F-actin was found to be weak and occur via a different mechanism. These results are relevant for understanding V10’s biological roles, at a molecular level, aiming at potential pharmacological applications.
- Binding modes of decavanadate to myosin and inhibition of the actomyosin ATPase activityPublication . Tiago, Teresa; Martel, Paulo; Gutiérrez-Merino, Carlos; Aureliano, M.Decavanadate, a vanadate oligomer, is known to interact with myosin and to inhibit the ATPase activity, but the putative binding sites and the mechanism of inhibition are still to be clarified. We have previously proposed that the decavanadate (V10O28 6−) inhibition of the actin-stimulated myosin ATPase activity is non-competitive towards both actin and ATP. A likely explanation for these results is that V10 binds to the so-called back-door at the end of the Pi-tube opposite to the nucleotide-binding site. In order to further investigate this possibility, we have carried out molecular docking simulations of the V10 oligomer on three different structures of the myosin motor domain of Dictyostelium discoideum, representing distinct states of the ATPase cycle. The results indicate a clear preference of V10 to bind at the back-door, but only on the “open” structures where there is access to the phosphate binding-loop. It is suggested that V10 acts as a “back-door stop” blocking the closure of the 50- kDa cleft necessary to carry out ATP-γ-phosphate hydrolysis. This provides a simple explanation to the non-competitive behavior of V10 and spurs the use of the oligomer as a tool to elucidate myosin back-door conformational changes in the process of muscle contraction.
- Biological activity of gold compounds against viruses and parasitosis: a systematic reviewPublication . Fonseca, Custódia; Aureliano, M.In this contribution, we provide an overview of gold compound applications against viruses or parasites during recent years. The special properties of gold have been the subject of intense investigation in recent years, which has led to the development of its chemistry with the synthesis of new compounds and the study of its applicability in various areas such as catalysis, materials, nanotechnology and medicine. Herein, thirteen gold articles with applications in several viruses, such as hepatitis C virus (HCV), influenza A virus (H1N1), vesicular stomatitis virus (VSV), coronavirus (SARS-CoV and SARS-CoV-2), Dengue virus, and several parasites such as Plasmodium sp., Leishmania sp., Tripanossoma sp., Brugia sp., Schistosoma sp., Onchocerca sp., Acanthamoeba sp., and Trichomonas sp. are described. Gold compounds with anti-viral activity include gold nanoparticles with the ligands mercaptoundecanosulfonate, 1-octanethiol and aldoses and gold complexes with phosphine and carbene ligands. All of the gold compounds with anti-parasitic activity reported are gold complexes of the carbene type. Auranofin is a gold drug already used against rheumatoid arthritis, and it has also been tested against virus and parasites.
- Biological effects of decavanadate: muscle contraction, in vivo oxidative stress, and mitochondrial toxicityPublication . Aureliano, M.Decameric vanadate species (V10) can be formed at physiological pH values in vanadate solutions presumably containing only monomeric vanadate species (V1). Sarcoplasmic reticulum Ca2+-ATPase and myosin are known to interact with decameric vanadate species. V10 interaction with myosin is favored by conformational changes that takes place in myosin during the catalytic cycle. Apparently, V10 operates at a different protein state in comparison to monomeric vanadate (V1) that mimics the protein at the hydrolysis transition state. V10 also clearly differs from V1, by inhibiting sarcoplasmic reticulum calcium accumulation in non-damage native vesicles, besides affecting calcium efflux associated with ATP synthesis and proton ejection associated with ATP hydrolysis. Recently reported studies referred that V10 is stabilized by actin during the process of the protein polymerization since the decomposition half-life time increases from 5 to 27 hours, suggesting that the interaction is also support by a protein conformation induce during ATP hydrolysis followed by the formation of protein filaments. Besides affecting muscle contraction and its regulation, V10, as low as 100 nM, inhibits 50% of oxygen consumption in mitochondria, pointing that this organelle is a potential cellular target for V10, while a 100-fold higher concentration of V1 (10 µM) is needed to induce the same effect. Furthermore, in vivo studies have shown that following an acute exposure, decavanadate induced different changes, when compared to vanadate, on oxidative stress markers, vanadium intracellular accumulation as well as in lipid peroxidation. Putting it all together, it is suggested that the biological effects of decameric vanadate species contribute, at least in part, to the understanding of the versatility of vanadium biochemistry.
- A bioquímica na sociedadePublication . Aureliano, M.A Química Biológica, também conhecida por Bioquímica, é uma área do conhecimento que é cada vez mais importante nas sociedades contemporâneas. A Bioquímica, é uma ciência interdisciplinar que utiliza estratégias e métodos de muitas outras, desde a Física à Farmacologia.
- Cadmium and vanadate oligomers effects on methaemoglobin reductase activity from Lusitanian toadfish: in vivo and in vitro studiesPublication . Aureliano, M.Cadmium and two vanadate solutions as ‘metavanadate’ (containing ortho and metavanadate species) and ‘decavanadate’ (containing decameric species) (5 mM) were injected intraperitoneously in Halobatrachus didactylus (Lusitanian toadfish), in order to evaluate the effects of cadmium and oligomeric vanadate species on methaemoglobin reductase activity from fish red blood cells. Following short-term exposure (1 and 7 days), different changes were observed on enzyme activity. After 7 days of exposure, ‘metavanadate’ increased methaemoglobin reductase activity by 67% (P,0.05), whereas, minor effects were observed on enzymatic activity upon cadmium and ‘decavanadate’ administration. However, in vitro studies indicate that decameric vanadate, in concentrations as low as 50mM, besides strongly inhibiting methaemoglobin reductase activity, promotes haemoglobin oxidation to methaemoglobin. Although decameric vanadate species showed to be unstable in the different media used in this work, the rate of decameric vanadate deoligomerization is in general slow enough, making it possible to study its effects. It is concluded that the increase in H.didactylus methaemoglobin reductase activity is more pronounced upon exposition to ‘metavanadate’ than to cadmium and decameric species. Moreover, only decameric vanadate species promoted haemoglobin oxidation, suggesting that vanadate speciation is important to evaluate in vivo and in vitro effects on methaemoglobin reductase activity.
- Characterization of decavanadate and decaniobate solutions by Raman spectroscopyPublication . Aureliano, M.; Ohlin, C. André; Vieira, Michele O.; Marques, M. Paula M.; Casey, William H.; Batista de Carvalho, Luís A. E.The decaniobate ion, (Nb10 = [Nb10O28]6−) being isoelectronic and isostructural with the decavanadate ion (V10 = [V10O28]6−), but chemically and electrochemically more inert, has been useful in advancing the understanding of V10 toxicology and pharmacological activities. In the present study, the solution chemistry of Nb10 and V10 between pH 4 and 12 is studied by Raman spectroscopy. The Raman spectra of V10 show that this vanadate species dominates up to pH 6.45 whereas it remains detectable until pH 8.59, which is an important range for biochemistry. Similarly, Nb10 is present between pH 5.49 and 9.90 and this species remains detectable in solution up to pH 10.80. V10 dissociates at most pH values into smaller tetrahedral vanadate oligomers such as V1 and V2, whereas Nb10 dissociates into Nb6 under mildly (10 > pH > 7.6) or highly alkaline conditions. Solutions of V10 and Nb10 are both kinetically stable under basic pH conditions for at least two weeks and at moderate temperature. The Raman method provides a means of establishing speciation in the difficult niobate system and these findings have important consequences for toxicology activities and pharmacological applications of vanadate and niobate polyoxometalates.