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61.
Guilherme Menegon Arantes 《Proteins》2010,78(14):3017-3032
Cdc25 phosphatases involved in cell cycle checkpoints are now active targets for the development of anti‐cancer therapies. Rational drug design would certainly benefit from detailed structural information for Cdc25s. However, only apo‐ or sulfate‐bound crystal structures of the Cdc25 catalytic domain have been described so far. Together with previously available crystalographic data, results from molecular dynamics simulations, bioinformatic analysis, and computer‐generated conformational ensembles shown here indicate that the last 30–40 residues in the C‐terminus of Cdc25B are partially unfolded or disordered in solution. The effect of C‐terminal flexibility upon binding of two potent small molecule inhibitors to Cdc25B is then analyzed by using three structural models with variable levels of flexibility, including an equilibrium distributed ensemble of Cdc25B backbone conformations. The three Cdc25B structural models are used in combination with flexible docking, clustering, and calculation of binding free energies by the linear interaction energy approximation to construct and validate Cdc25B‐inhibitor complexes. Two binding sites are identified on top and beside the Cdc25B active site. The diversity of interaction modes found increases with receptor flexibility. Backbone flexibility allows the formation of transient cavities or compact hydrophobic units on the surface of the stable, folded protein core that are unexposed or unavailable for ligand binding in rigid and densely packed crystal structures. The present results may help to speculate on the mechanisms of small molecule complexation to partially unfolded or locally disordered proteins. Proteins 2010. © 2010 Wiley‐Liss, Inc. 相似文献
62.
Silva AC Morsch AL Zanin RF Corrêa MC Arantes LC Araujo MC Morsch VM Schetinger MR 《Biochimica et biophysica acta》2005,1741(3):282-288
The activities of the enzymes NTPDase (E.C.3.6.1.5, apyrase, ATP diphosphohydrolase, ecto-CD 39) and 5'-nucleotidase (E.C.3.1.3.5, CD 73) were analyzed in platelets from patients with chronic renal failure (CRF), both undergoing hemodialysis treatment (HD) and not undergoing hemodialysis (ND), as well as from a control group. The results showed an increase in platelet NTPDase activity in CRF patients on HD treatment (52.88%) with ATP as substrate (P<0.0001). ADP hydrolysis was decreased (33.68% and 39.75%) in HD and ND patients, respectively. In addition, 5'-nucleotidase activity was elevated in the HD (160%) and ND (81.49%) groups when compared to the control (P<0.0001). Significant correlation was found among ATP, ADP and AMP hydrolysis and plasma creatinine and urea levels (P<0.0001). Patients were compared statistically according the time of hemodialysis treatment. We found enhanced NTPDase and 5'-nucleotidase activities between 49 and 72 months on HD patients. Our result suggests the existence of alterations in nucleotide hydrolysis in platelets of CRF patients. Possibly, this altered nucleotide hydrolysis could contribute to hemostasis abnormalities found in CRF. 相似文献
63.
de Almeida L Cintra AC Veronese EL Nomizo A Franco JJ Arantes EC Giglio JR Sampaio SV 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2004,137(1):19-27
The high mortality caused by Crotalus durissus terrificus snake venom is mainly due to crotoxin, which acts on the neuromuscular junction inhibiting the mechanism mediating acetylcholine release, thus leading to motor and respiratory paralysis and subsequently to animal death. We recently demonstrated that the aqueous extract (AE) of Tabernaemontana catharinensis can inhibit the lethal activity of C. d. terrificus venom. Eight fractions, PI to PVIII, were obtained by gel filtration of the extract on Sephadex G-10, and assayed for lethality and cytotoxicity. Fraction PVII [2.0 mg/100 g rat/50 microl saline solution (ss)] injected intramuscularly (i.m.) 20 s after the venom (240 microg) or crotoxin (200 microg/50 microl ss) neutralized the lethal activity of 2 LD50 of both. Fractions PI, PVI and PVIII (5.0 mg/100 g rat/50 microl ss) presented potent antitumoral activity in vitro against cells from human breast carcinoma (SK-BR-3) after 24 h incubation, as measured by Mosmann colorimetric method. Fraction PVII contains 12-methoxy-4-methylvoachalotine as its major component. These results demonstrate that the antivenom and antitumoral activities of the AE of T. catharinensis are exerted by different substances present in fraction PVII and fractions PI, PVI and PVIII, respectively, whose characteristics are distinct in terms of staining and Rf when analyzed by thin layer chromatography. The results also show that a preliminary fractionation by Sephadex G-10 gel filtration is a good option as a first step for isolation of biologically active substances from T. catharinensis. 相似文献
64.
Ana Flávia Mar?al-Pessoa Carmen Lucia Bassi-Branco Cristiana dos Santos Barbosa Salvatierra Luiz Fabrizio Stoppiglia Letícia Martins Ignacio-Souza Sílvia Regina de Lima Reis Roberto Vilela Veloso Marise Auxiliadora de Barros Reis Everardo Magalh?es Carneiro Antonio Carlos Boschero Vanessa Cristina Arantes Márcia Queiroz Latorraca 《Biological research》2015,48(1)
Background
Gap junctions between β-cells participate in the precise regulation of insulin secretion. Adherens junctions and their associated proteins are required for the formation, function and structural maintenance of gap junctions. Increases in the number of the gap junctions between β-cells and enhanced glucose-stimulated insulin secretion are observed during pregnancy. In contrast, protein restriction produces structural and functional alterations that result in poor insulin secretion in response to glucose. We investigated whether protein restriction during pregnancy affects the expression of mRNA and proteins involved in gap and adherens junctions in pancreatic islets. An isoenergetic low-protein diet (6% protein) was fed to non-pregnant or pregnant rats from day 1–15 of pregnancy, and rats fed an isocaloric normal-protein diet (17% protein) were used as controls.Results
The low-protein diet reduced the levels of connexin 36 and β-catenin protein in pancreatic islets. In rats fed the control diet, pregnancy increased the levels of phospho-[Ser279/282]-connexin 43, and it decreased the levels of connexin 36, β-catenin and beta-actin mRNA as well as the levels of connexin 36 and β-catenin protein in islets. The low-protein diet during pregnancy did not alter these mRNA and protein levels, but avoided the increase of levels of phospho-[Ser279/282]-connexin 43 in islets. Insulin secretion in response to 8.3 mmol/L glucose was higher in pregnant rats than in non-pregnant rats, independently of the nutritional status.Conclusion
Short-term protein restriction during pregnancy prevented the Cx43 phosphorylation, but this event did not interfer in the insulin secretion. 相似文献65.
BK McFarlin AS Venable RR Williams AW Jackson 《Biology of sport / Institute of Sport》2015,32(1):11-14
Exercising or working in a hot, humid environment can results in the onset of heat-related illness when an individual''s temperature is not carefully monitored. The purpose of the present study was to compare three techniques (data loggers, thermal imaging, and wired electrodes) for the measurement of peripheral (bicep) and central (abdominal) skin temperature. Young men and women (N = 30) were recruited to complete the present study. The three skin temperature measurements were made at 0 and every 10-min during 40-min (60% VO2max) of cycling in a hot (39±2°C), humid (45±5% RH) environment. Data was statistically analyzed using the Bland-Altman method and correlation analysis. For abdominal skin temperature, the Bland-Altman limits of agreement indicated that data loggers (1.5) were a better index of wired than was thermal imaging (3.5), For the bicep skin temperature the limits of agreement was similar between data loggers (1.9) and thermal (1.9), suggesting the both were suitable measurements. We also found that when skin temperature exceeded 35°C, we observed progressively better prediction between data loggers, thermal imaging, and wired skin sensors. This report describes the potential for the use of data loggers and thermal imaging to be used as alternative measures of skin temperature in exercising, human subjects. 相似文献
66.
Gabriel Arantes dos Santos Ruan Pimenta Nayara I. Viana Vanessa R. Guimarães Poliana Romão Patrícia Candido Juliana A. de Camargo Diná M. Hatanaka Paula GS. Queiroz Alexandre Teruya Katia R.M. Leite Victor Srougi Miguel Srougi Sabrina T. Reis 《Biochemistry and Biophysics Reports》2021
The infection by COVID-19 is a serious global public health problem. An efficient way to improve this disease's clinical management would be to characterize patients at higher risk of progressing to critically severe infection using prognostic biomarkers. The telomere length could be used for this purpose. Telomeres are responsible for controlling the number of maximum cell divisions. The telomere length is a biomarker of aging and several diseases. We aimed to compare leukocyte telomere length (LTL) between patients without COVID-19 and patients with different clinical severity of the infection. Were included 53 patients who underwent SARS-CoV-2 PCR divided in four groups. The first group was composed by patients with a negative diagnosis for COVID-19 (n = 12). The other three groups consisted of patients with a confirmed diagnosis of COVID-19 divided according to the severity of the disease: mild (n = 15), moderate (n = 17) and severe (n = 9). The LTL was determined by Q-PCR. The severe group had the shortest LTL, followed by the moderate group. The negative and mild groups showed no differences. There is an increase of patients with hypertension (p = 0.0099) and diabetes (p = 0.0067) in moderate and severe groups. Severe group was composed by older patients in comparison with the other three groups (p = 0.0083). Regarding sex, there was no significant difference between groups (p = 0.6279). In an ordinal regression model, only LTL and diabetes were significantly associated with disease severity. Shorter telomere length was significantly associated with the severity of COVID-19 infection, which can be useful as a biomarker or to better understand the SARS-CoV-2 pathophysiology. 相似文献
67.
Kátia Daniela Silveira Lívia Corrêa Barroso Angélica Thomáz Vieira Daniel Cisalpino Cristiano Xavier Lima Michael Bader Rosa Maria Esteves Arantes Robson Augusto Souza dos Santos Ana Cristina Sim?es-e-Silva Mauro Martins Teixeira 《PloS one》2013,8(6)
Angiotensin-(1–7) [Ang-(1–7)] is a biologically active heptapeptide that may counterbalance the physiological actions of angiotensin II (Ang II) within the renin-angiotensin system (RAS). Here, we evaluated whether activation of the Mas receptor with the oral agonist, AVE 0991, would have renoprotective effects in a model of adriamycin (ADR)-induced nephropathy. We also evaluated whether the Mas receptor contributed for the protective effects of treatment with AT1 receptor blockers. ADR (10 mg/kg) induced significant renal injury and dysfunction that was maximal at day 14 after injection. Treatment with the Mas receptor agonist AVE 0991 improved renal function parameters, reduced urinary protein loss and attenuated histological changes. Renoprotection was associated with reduction in urinary levels of TGF-β. Similar renoprotection was observed after treatment with the AT1 receptor antagonist, Losartan. AT1 and Mas receptor mRNA levels dropped after ADR administration and treatment with losartan reestablished the expression of Mas receptor and increased the expression of ACE2. ADR-induced nephropathy was similar in wild type (Mas+/+) and Mas knockout (Mas
−/−) mice, suggesting there was no endogenous role for Mas receptor activation. However, treatment with Losartan was able to reduce renal injury only in Mas+/+, but not in Mas
−/− mice. Therefore, these findings suggest that exogenous activation of the Mas receptor protects from ADR-induced nephropathy and contributes to the beneficial effects of AT1 receptor blockade. Medications which target specifically the ACE2/Ang-(1–7)/Mas axis may offer new therapeutic opportunities to treat human nephropathies. 相似文献
68.
In this paper, we present the responses of the white-rot fungus Perenniporia medulla-panis to iron availability with regard to alterations in growth, expression of cellular proteins, Fe3+-reducing activity, and Fe3+ chelators production. Iron supplementation stimulated fungal growth but did not result in a significant increase in biomass production. Catechol and hydroxamate derivatives were produced mainly under iron deficiency, and their productions were repressed under iron supplementation conditions. Perenniporia medulla-panis showed several cellular proteins in the range of 10-90 kDa. Some of them showed negative iron-regulation. Iron-supplemented medium also repressed both cell surface and extracellular Fe3+-reducing activities; however, the highest cell surface activity was detected at the initial growth phase, whereas extracellular activity increased throughout the incubation period. No significant production of chelators and extracellular Fe3+-reducing activity were observed within the initial growth phase, suggesting that the reduction of Fe3+ to Fe2+ is performed by ferrireductases. 相似文献
69.
Gabriel Gustinelli Arantes de Carvalho Iracema Alves Manoel Degaspari Vasco Branco João Canário Alberto Ferreira de Amorim Valerie Helen Kennedy José Roberto Ferreira 《Biological trace element research》2014,159(1-3):128-134
Mercury occurrence was evaluated in samples of edible muscle tissue of 27 blue sharks (Prionace glauca) caught in the Atlantic Ocean, adjacent to the south and southeastern Brazilian coast, indicating a slight increase in comparison with previous data obtained for the same studied area and being higher than those fish caught at different sites of the Atlantic Ocean. Total Hg concentrations ranged from 0.46 to 2.40 mg kg?1 with the organic Hg fraction ranging between 0.44 and 2.37 mg kg?1. A negative correlation between total Hg concentration in muscle tissue and blue shark size was obtained, and 40 % of samples analyzed had Hg concentrations higher than 1.0 mg kg?1 Hg, the maximum concentration permitted in Brazilian predator fish. Data obtained showed that total Hg can be used as a reliable predictor of organic Hg in blue shark muscle because 95 to 98 % of the total Hg measured was found to be organic mercury. The wide range of Hg concentrations obtained for our set of samples can be explained by the heterogeneity of sampled population and the large size of the studied area. Given the adverse toxicological effects of Hg on animals and humans, a regular monitoring program of Hg contamination in Brazilian marine ecosystem can be recommended. 相似文献
70.
Mariani Carla Prudente Batista Eliane de Fatima Duarte Michele Delarmelina dos Reis Borba Emilie Zingler João Mangussi-Gomes Beatriz Taynara Araújo dos Santos Olivia Laquis de Moraes Sylvia Asaka Yamashita Hayashida Edmund C. Baracat Francisco de Assis da Rocha Neves Gustavo Arantes Rosa Maciel Tania Aparecida Sartori Sanchez Bachega Gustavo Barcelos Barra Adriana Lofrano-Porto 《Gene》2014