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61.
Chiara Ciaccio Alessandra Pesce Grazia R. Tundo Lesley Tilleman Laura Bertolacci Sylvia Dewilde Luc Moens Paolo Ascenzi Martino Bolognesi Marco Nardini Massimo Coletta 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(9):1813-1823
Functional and structural properties of protoglobin from Methanosarcina acetivorans, whose Cys(101)E20 residue was mutated to Ser (MaPgb*), and of mutants missing either the first 20 N-terminal amino acids (MaPgb*-ΔN20 mutant), or the first 33 N-terminal amino acids [N-terminal loop of 20 amino acids and a 13-residue Z-helix, preceding the globin fold A-helix; (MaPgb*-ΔN20Z mutant)] have been investigated. In keeping with the MaPgb*-ΔN20 mutant crystal structure, here reported at 2.0 Å resolution, which shows an increased exposure of the haem propionates to the solvent, the analysis of ligand binding kinetics highlights high accessibility of ligands to the haem pocket in ferric MaPgb*-ΔN20. CO binding to ferrous MaPgb*-ΔN20 displays a marked biphasic behavior, with a fast binding process close to that observed in MaPgb* and a slow carbonylation process, characterized by a rate-limiting step. Conversely, removal of the first 33 residues induces a substantial perturbation of the overall MaPgb* structure, with loss of α-helical content and potential partial collapse of the protein chain. As such, ligand binding kinetics are characterized by very slow rates that are independent of ligand concentration, this being indicative of a high energy barrier for ligand access to the haem, possibly due to localized misfolding. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins. 相似文献
62.
Cécile Faure Béatrice Morio Philippe Chafey Servane Le Plénier Philippe Noirez Voahangy Randrianarison‐Huetz Luc Cynober Christian Aussel Christophe Moinard 《Proteomics》2013,13(14):2191-2201
Citrulline (Cit) actions on muscle metabolism remain unclear. Those latter were investigated using a proteomic approach on Tibialis muscles from male Sprague‐Dawley rats. At 23 months of age, rats were either fed ad libitum (AL group) or subjected to dietary restriction for 12 weeks. At the end of the restriction period, one group of rats was euthanized (R group) and two groups were refed for one week with a standard diet supplemented with nonessential amino acids group or Cit (CIT group). Results of the proteomic approach were validated using targeted Western blot analysis and assessment of gene expression of the related genes. Maximal activities of the key enzymes involved in mitochondrial functioning were also determined. Cit supplementation results in a significant increase in the protein expression of the main myofibrillar constituents and of a few enzymes involved in glycogenolysis and glycolysis (CIT vs. AL and R, p < 0.05). Conversely, the expression of oxidative enzymes from Krebs cycle and mitochondrial respiratory chain was significantly decreased (CIT vs. AL, p < 0.05). However, maximal activities of key enzymes of mitochondrial metabolism were not significantly affected, except for complex 1 which presented an increased activity (CIT vs. AL and R, p < 0.05). In conclusion, Cit supplementation increases expression of the main myofibrillar proteins and seems to induce a switch in muscle energy metabolism, from aerobia toward anaerobia. 相似文献
63.
64.
Géraldine De Muylder Sylvie Daulouède Laurence Lecordier Pierrick Uzureau Yannick Morias Jan Van Den Abbeele Guy Caljon Michel Hérin Philippe Holzmuller Silla Semballa Pierrette Courtois Luc Vanhamme Beno?t Stijlemans Patrick De Baetselier Michael P. Barrett Jillian L. Barlow Andrew N. J. McKenzie Luke Barron Thomas A. Wynn Alain Beschin Philippe Vincendeau Etienne Pays 《PLoS pathogens》2013,9(10)
Background
In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells.Methodology/Principal findings
By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO) synthase activity. This TbKHC1 activity was IL-4Rα-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1-mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time.Conclusion
A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity. 相似文献65.
Emilio García García María-Ángeles Vázquez López Rafael Galera Martínez Irene Alias Manuel Martín González Antonio Bonillo Perales José Eugenio Cabrera Sevilla Icíar García Escobar Sara Gómez Bueno Encarnación López Ruzafa Francisco-Javier Muñoz Vico Patricia Oliva Pérez María Ortiz Pérez Juan Poveda González Marisa Rodríguez Lucenilla Firma-Isabel Rodríguez Sánchez Ana Ruiz Sánchez Lucía Ruiz Tudela Sara Torrico 《Endocrinología y nutrición》2013,60(3):121-126
ObjectivesTo estimate the prevalence of obesity and overweight in children and adolescents in our city and to investigate the associated factors.Subjects and methodsA cross-sectional study of 1317 children and adolescents aged 2-16 years. Multistage probability sampling was used to select three groups of subjects: 411 aged 12 to 16 years, 504 aged 6 to 12 years, and 402 aged 2 to 6 years. Body mass index was calculated, and obesity and overweight were diagnosed using the threshold levels of the International Obesity Task Force for children and adolescents. Parents were asked about eating habits, health, social, and demographic aspects. Results are given as percentages (95% confidence interval). The relationship between obesity and overweight and the different variables was studied using multiple logistic regression. The adjusted odds ratio (OR) was calculated.ResultsAmong children and adolescentes aged 2-16 years, 9.5% (8.0%-11.0%) were obese and 22.4% (23.3%-24.6%) were overweight. Of subjects aged 12-16 years, 8.5% (5.9%-11.2%) were obese and 20.5% (16.7%-24.3%) were overweight. In the groups aged 6-12 years and 2-6 years, rates of obesity and overweight were 11.6% (8.9% -14.3%) and 31.0% (27.0-35.0) and 8.0% (5.4%-10.6%) and 13.6% (10.3%-16.9%) respectively. Obesity or overweight was associated to age (OR 1.21; P< 0.001), maternal obesity (OR 10.99; P= 0.008), a birthweight higher than 4 kg (OR 2.91; p 0.002), and formula feeding (OR 1.82; P= 0.005).ConclusionObesity and overweight in children and adolescents are highly prevalent problems in our city. 相似文献
66.
Julie Lorin Jean-Claude Guilland Claudia Korandji Claude Touzery Florence Bichat Aline Chagnon Yves Cottin Luc Rochette Catherine Vergely Marianne Zeller 《PloS one》2013,8(6)
Objectives
Low levels of high-density lipoprotein (HDL) cholesterol are associated with an increased risk of acute myocardial infarction possibly through impaired endothelial atheroprotection and decreased nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA) mediates endothelial function by inhibiting nitric oxide synthase activity. In patients with acute myocardial infarction, we investigated the relationship between serum levels of HDL and ADMA.Approach and Results
Blood samples from 612 consecutive patients hospitalized for acute MI <24 hours after symptom onset were taken on admission. Serum levels of ADMA, its stereoisomer, symmetric dimethylarginine (SDMA) and L-arginine were determined using high-performance liquid chromatography. Patients with low HDL (<40 mg/dL for men and <50 mg/dL for women) were compared with patients with higher HDL. Most patients (59%) had low HDL levels. Median ADMA levels were markedly higher in the low HDL group (0.69 vs. 0.50 µmole/L, p<0.001). In contrast, SDMA and L-arginine levels were similar for the two groups (p = 0.120 and p = 0.064). Notably, ADMA, but not SDMA or L-arginine, was inversely correlated with HDL (r = −0.311, p<0.001). In stratified analysis, this relationship was only found for low HDL levels (r = −0.265, p<0.001), but not when HDL levels were higher (r = −0.077, p = 0.225). By multivariate logistic regression analysis, ADMA level was strongly associated with low HDL levels (OR(95%CI):6.06(3.48–10.53), p<0.001), beyond traditional confounding factors.Conclusions
Our large population-based study showed for the first time a strong inverse relationship between HDL and ADMA in myocardial infarction patients, suggesting a functional interaction between HDL and endothelium, beyond metabolic conditions associated with low HDL levels. 相似文献67.
Xavier Fioramonti Adam Deak Srinidhi Deshpande Lionel Carneiro Chunxue Zhou Nazish Sayed Branly Orban Joshua R. Berlin Luc Pénicaud Corinne Leloup Annie Beuve Vanessa H. Routh 《PloS one》2013,8(7)
Aims
Hypoglycemia is a severe side effect of intensive insulin therapy. Recurrent hypoglycemia (RH) impairs the counter-regulatory response (CRR) which restores euglycemia. During hypoglycemia, ventromedial hypothalamus (VMH) production of nitric oxide (NO) and activation of its receptor soluble guanylyl cyclase (sGC) are critical for the CRR. Hypoglycemia also increases brain reactive oxygen species (ROS) production. NO production in the presence of ROS causes protein S-nitrosylation. S-nitrosylation of sGC impairs its function and induces desensitization to NO. We hypothesized that during hypoglycemia, the interaction between NO and ROS increases VMH sGC S-nitrosylation levels and impairs the CRR to subsequent episodes of hypoglycemia. VMH ROS production and S-nitrosylation were quantified following three consecutive daily episodes of insulin-hypoglycemia (RH model). The CRR was evaluated in rats in response to acute insulin-induced hypoglycemia or via hypoglycemic-hyperinsulinemic clamps. Pretreatment with the anti-oxidant N-acetyl-cysteine (NAC) was used to prevent increased VMH S-nitrosylation.Results
Acute insulin-hypoglycemia increased VMH ROS levels by 49±6.3%. RH increased VMH sGC S-nitrosylation. Increasing VMH S-nitrosylation with intracerebroventricular injection of the nitrosylating agent S-nitroso-L-cysteine (CSNO) was associated with decreased glucagon secretion during hypoglycemic clamp. Finally, in RH rats pre-treated with NAC (0.5% in drinking water for 9 days) hypoglycemia-induced VMH ROS production was prevented and glucagon and epinephrine production was not blunted in response to subsequent insulin-hypoglycemia.Conclusion
These data suggest that NAC may be clinically useful in preventing impaired CRR in patients undergoing intensive-insulin therapy. 相似文献68.
Giovanni Monaco Elke Decrock Koen Nuyts Larry E. Wagner II Tomas Luyten Sergei V. Strelkov Ludwig Missiaen Wim M. De Borggraeve Luc Leybaert David I. Yule Humbert De Smedt Jan B. Parys Geert Bultynck 《PloS one》2013,8(8)
The anti-apoptotic Bcl-2 protein is the founding member and namesake of the Bcl-2-protein family. It has recently been demonstrated that Bcl-2, apart from its anti-apoptotic role at mitochondrial membranes, can also directly interact with the inositol 1,4,5-trisphosphate receptor (IP3R), the primary Ca2+-release channel in the endoplasmic reticulum (ER). Bcl-2 can thereby reduce pro-apoptotic IP3R-mediated Ca2+ release from the ER. Moreover, the Bcl-2 homology domain 4 (Bcl-2-BH4) has been identified as essential and sufficient for this IP3R-mediated anti-apoptotic activity. In the present study, we investigated whether the reported inhibitory effect of a Bcl-2-BH4 peptide on the IP 3R1 was related to the distinctive α-helical conformation of the BH4 domain peptide. We therefore designed a peptide with two glycine “hinges” replacing residues I14 and V15, of the wild-type Bcl-2-BH4 domain (Bcl-2-BH4-IV/GG). By comparing the structural and functional properties of the Bcl-2-BH4-IV/GG peptide with its native counterpart, we found that the variant contained reduced α-helicity, neither bound nor inhibited the IP 3R1 channel, and in turn lost its anti-apoptotic effect. Similar results were obtained with other substitutions in Bcl-2-BH4 that destabilized the α-helix with concomitant loss of IP3R inhibition. These results provide new insights for the further development of Bcl-2-BH4-derived peptides as specific inhibitors of the IP3R with significant pharmacological implications. 相似文献
69.
Fish models are essential for research in many biological and medical disciplines. With a typical lifespan of only 6 months, the Turquoise killifish (Nothobranchius furzeri) was recently established as a time- and cost-efficient model to facilitate whole-life and multigenerational studies in several research fields, including behavioural ecotoxicology. Essential information on the behavioural norm and on how laboratory conditions affect behaviour, however, is deficient. In the current study, we examined the impact of the social and structural environment on a broad spectrum of behavioural endpoints in N. furzeri. While structural enrichment affected only fish boldness and exploratory behaviour, fish rearing density affected the total body length, locomotor activity, boldness, aggressiveness and feeding behaviour of N. furzeri individuals. Overall, these results contribute to compiling a behavioural baseline for N. furzeri that increases the applicability of this new model species. Furthermore, our findings will fuel the development of improved husbandry protocols to maximize the welfare of N. furzeri in a laboratory setting. 相似文献
70.
García-Tuñón Ignacio Vuelta Elena Lozano Laura Herrero María Méndez Lucía Palomero-Hernandez Javier Pérez-Caro María Pérez-García Jessica González-Sarmiento Rogelio Sánchez-Martín Manuel 《Molecular biology reports》2020,47(2):1381-1391
Molecular Biology Reports - The Nomo1 gene mediates a wide range of biological processes of importance in embryonic development. Accordingly, constitutive perturbation of Nomo1 function may result... 相似文献