119 resultados para inosine monophosphate dehydrogenase


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Tropidurid lizards have colonized a variety of Brazilian open environments without remarkable morphological variation, despite ecological and structural differences among habitats used. This study focuses on two Tropidurus sister-species that, despite systematic proximity and similar morphology, exhibit great ecological divergence and a third ecologically generalist congeneric species providing an outgroup comparison. We quantified jumping capacity and sprint speed of each species on sand and rock to test whether ecological divergence was also accompanied by differences in locomotor performance. Relevant physiological traits possibly associated with locomotor performance metabolic scopes and fiber type composition, power output and activity of the enzymes citrate synthase, pyruvate kinase and lactate dehydrogenase of the iliofibularis muscle - were also compared among the three Tropidurus species. We found that the two sister-species exhibited remarkable differences in jumping performance, while Tropidurus oreadicus, the more distantly related species, exhibited intermediate values. Tropidurus psamonastes, a species endemic to sand dunes, exhibited high absolute sprint speeds on sand, jumped rarely and possessed a high proportion of glycolytic fibers and low activity of citrate synthase. The sister-species Tropidurus itambere, endemic to rocky outcrops, performed a large number of jumps and achieved lower absolute sprint speed than T. psamonastes. This study provides evidence of rapid divergence of locomotor parameters between sister-species that use different substrates, which is only partially explained by variation in physiological parameters of the iliofibularis muscle.

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The tropical mosquito Aedes aegypti (Diptera: Culicidae) is the most important domestic vector of urban yellow fever and dengue viruses. Ae. aegypti originated from Africa and was probably introduced into Brazil during the colonial period through embarkations, and dengue epidemics soon followed. Genetic analysis of 12 Ae. aegypti populations from five states in Brazil was conducted based on two mitochondrial DNA fragments: cytochrome oxidase I and NADH dehydrogenase subunit 4. Analyses comparing individual haplotypes indicated the existence of two well-defined clades, probably representing two mitochondrial lineages. Analysis of molecular variance showed significant variability in genetic structure among collections within groups. Mantel regression analysis showed a correlation between genetic and geographic distances, mainly because of northern and northeastern populations, in comparison with those in the southeast. The population from Santos, the largest port in Brazil, showed the greatest diversity, with 10 unique haplotypes, an indication of recent introductions that have not yet spread to other Brazilian cities. Different mitochondrial DNA sequences were found in three specimens, indicating the presence of heteroplasmy.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Recent lines of evidences indicate that several pathological conditions, as cardiovascular diseases, are associated with oxidative stress. In order to validate a butylated hydroxytoluene (BHT)-induced experimental model of oxidative stress in the cardiac tissue and serum lipids, 12 Wistar rats were divided into two groups, a control group and the BHT group, Which received BHT i.p. twice a week (1500 mg/kg body Weight) during 30 days. BHT group presented lower body weight gain and heart weight. BHT induced toxic effects on serum through increased triacylglycerols (TG), VLDL and LDL-cholesterol concentrations. The heart of BHT animals showed alteration of antioxidant defenses and increased concentrations of lipid hydroperoxides, indicating elevated lipoperoxidation. TG concentrations and lactate dehydrogenase activities were elevated in the cardiac Muscle of BHT animals. Thus, long-term administration of BHT is capable to induce oxidative and metabolic alterations similarly to some pathological disorders, constituting an efficient experimental model to health scientific research. (c) 2005 Elsevier GrnbH. All rights reserved.

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The present study examined the interaction of hypercaloric diet (HD) and physical exercise on lipid profile and oxidative stress in serum and liver of rats. Male Wistar rats (60-days-old) were fed with a control (C) and hypercaloric diet (H). Each of the two dietary groups (C and H) was divided into three subgroups (n = 8), sedentary (CS and HS), exercised 2 days a week (CE2 and HE2) and exercised 5 days a week (CE5 and HE5). The swimming was selected as a model for exercise performance. After 8-weeks exercised rats showed decreased lactate dehydrogenase serum activities, demonstrating the effectiveness of the swimming as an aerobic-training protocol. Exercise 5-days a week reduced the body weight gain. Triacylglycerol (TG) and very low-density lipoprotein (VLDL-C) were increased in HD-fed rats. HE5 and CE5 rats had decreased TG, VLDL-C and cholesterol. HE2 rats had enhanced high-density lipoprotein (HDL-C) in serum. No alterations were observed in lipid hydroperoxide (LH), while total antioxidant substances (TAS) were increased in serum of exercised rats. HD-fed rats had hepatic TG accumulation. Superoxide dismutase activities were increased and catalase was decreased in liver of exercised rats. The interaction of HD and physical exercise reduced TAS and enhanced LH levels in hepatic tissue. In conclusion, this study confirmed the beneficial effect of physical exercise as a dyslipidemic-lowering component. Interaction of HD and physical exercise had discrepant effects on serum and liver oxidative stress. The interaction of HID and physical exercise reduced the oxidative stress in serum. HD and physical exercise interaction had pro-oxidant effect on hepatic tissue, suggesting that more studies should be done before using physical exercise as an adjunct therapy to reduce the adverse effects of HD. (c) 2006 Elsevier Ltd. All rights reserved.

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Water contaminants have a high potential risk for the health of populations. Protection from toxic effects of environmental water pollutants primarily involves considering the mechanism of low level toxicity and likely biological effects in organisms who live in these polluted waters. The biomarkers assessment of oxidative stress and metabolic alterations to cadmium exposure were evaluated in Nile tilapia, Oreochromis niloticus. The fish were exposed to 0.35, 0.75, 1.5, and 3.0 mg/l concentrations of Cd2+ (CdCl2) in water for 60 days. Fish that survived cadmium exposure showed a metabolic shift and a compensatory development for maintenance of the body weight gain. We observed a decreased glycogen content and decreased glucose uptake in white muscle. Lactate dehydrogenase (LDH) and creatine phosphokinase (CK) activities were also decreased, indicating that the glycolytic capacity was decreased in this tissue. No alterations were observed in total protein content in white muscle due to cadmium exposure suggesting a metabolic shift of carbohydrate metabolism to maintenance of the muscle protein reserve. There was an increase in glucose uptake, CK increased activity, and a clear increase of LDH activity in red muscle of fish with cadmium exposure. Since no alterations were observed in lipoperoxide concentration, while antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were changed in the liver and the red and white muscle of fish with cadmium exposure, we can conclude that oxygen free radicals are produced as a mediator of cadmium toxicity. Resistance development is related with increased activities of antioxidant enzymes, which were important in the protection against cadmium damage, inhibiting lipoperoxide formation. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

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Contamination with cadmium compounds poses high potential risk for the health of populations and for this reason the treatment of their toxic effects should urgently be established. The present study was carried out to determine whether or-tocopherol intake can protect tissues against damage induced by cadmium, and to clarify the contribution of superoxide radicals (O-2(-)) in this process. Cadmium chloride was tested for tissue damage by a single intraperitoneal injection of Cd2+ ions (2 mg Kg(-1)). To determine the potential therapeutic effect of Vitamin E, a group of Cd2+-treated rats received a drinking solution of or-tocopherol (40 mg l(-1)) for 15 days. Cadmium induced increased serum creatinine and total lactate dehydrogenase, reflecting renal and cardiac damage. The increased lipoperoxide and decreased Cu-Zn superoxide dismutase levels indicated the generation of superoxide radicals in cadmium-treated rats. Tocopherol induced increased serum high-density lipoprotein and depressed the toxic effects of Ca2+ alone, since creatinine and lactate dehydrogenase determinations were recovered to the control values. Tocopherol decreased lipoperoxide and led the superoxide dismutase activities to approach those of the control values. We concluded that superoxide radicals are produced as mediators of cadmium toxicity. Tocopherol possesses a significant anti-radical activity and inhibits the cadmium effect on superoxide dismutase activity. Tocopherol also protected tissues from the toxic effects of cadmium by a direct antioxidant action which decreased lipoperoxide formation.

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This study examined whether sucrose-rich diet (SRD)-induced hyperglycaemia, dyslipidemia and oxidative stress may be inhibited by N-acetylcysteine (C5H9-NO3S), an organosulfur from Allium plants. Male Wistar 40 rats were divided into four groups (n = 10): (C) given standard chow and water; (N) receiving standard chow and 2 mg/l N-acetylcysteine in its drinking water; (SRD) given standard chow and 30% sucrose in its drinking water; and (SRD-N) receiving standard chow, 30% sucrose and N-acetylcysteine in its drinking water. After 30 days of treatment, SRD rats had obesity with increased abdominal circumference, hyperglycaemia, by dyslipidemia and hepatic triacylglycerol accumulation. These adverse effects were associated with oxidative stress and depressed lipid degradation in hepatic tissue. The SRD adverse effects were not observed in SDR-N rats. N-Acetylcysteine reduced the oxidative stress, enhancing glutathione-peroxidase activity, and normalizing lipid hydroperoxyde, reduced glutathione and superoxide dismutase in hepatic tissue of SRD-N rats. The beta-hydroxyacyl coenzyme-A dehydrogenase and citrate-synthase activities were increased in SRD-N rats, indicating enhanced lipid degradation in hepatic tissue as compared to SRD. SRD-N rats had reduced serum oxidative stress and diminished glucose, triacylglycerol, very-low-density lipoprotein (VLDL), oxidized low-density lipoprotein (alpha-LDL) and cholesterol/highdensity lipoprotein (HDL) ratio in relation to SRD. In conclusion, NAC offers promising therapeutic values in prevention of dyslipidemic profile and alleviation of hyperglycaemia in high-sucrose intake condition by improving antioxidant defences. N-Acetylcysteine had also effects preventing metabolic shifting in hepatic tissue, thus enhancing fat degradation and reducing body weight gain in conditions of excess sucrose intake. The application of this agent in food system via exogenous addition may be feasible and beneficial for antioxidant protection. (c) 2006 Elsevier B.V All rights reserved.

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The present study was carried out to investigate the effects of copper (Cu) intake on lipid profile, oxidative stress and tissue damage in normal and in diabetic condition. Since diabetes mellitus is a situation of high-risk susceptibility to toxic compounds, we examined potential early markers of Cu excess in diabetic animals. Male Wistar rats, at 60-days-old were divided into six groups of eight rats each. The control(C) received saline from gastric tube, the no-diabetic(Cu-10), treated with 10 mg/kg of Cu(Cu(++)-CuSO(4), gastric tube), no-diabetic with Cu-60mg/kg(Cu-60), diabetic(D), diabetic low-Cu(DCu-10) and diabetic high-Cu(DCu-60). Diabetes was induced by an ip injection of streptozotocin (60mg/kg). After 30 days of treatments, no changes we're observed in serum lactate dehydrogenase, alanine transaminase and alkaline phosphatase; indicating no adverse effects on cardiac and hepatic tissues. D-rats had glucose intolerance and dyslipidemic profile. Cholesterol and LDL-cholesterol were higher in Cu-60 and DCu-60 than in C, Cu-10 and D and DCu-10 groups respectively. Cu-60 rats had higher lipid hydroperoxide (HP) and lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) serum activities than C and Cu-10 rats. LH was increased and GSH-Px was decreased, while no alterations were observed in SOD and catalase in serum of DCu-60 animals. DCu-60 rats had increased urinary glucose, creatinine and albumin. In conclusion, Cu intake at high concentration induced adverse effects on lipid profile, associated with oxidative stress and diminished activities of antioxidant enzymes. Diabetic animals were more susceptible to copper toxicity. High Cu intake induced dyslipidemic profile, oxidative stress and kidney dysfunction in diabetic condition. Copper renal toxicity was associated with oxidative stress and reduction at least, one of the antioxidant enzymes. (C) 2004 Elsevier Ltd. All rights reserved.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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The delimitation of cryptic species within the main vector of the American visceral leishmaniasis, Lutzomyia longipalpis, remains a topic of controversy. An analysis of generic variability based on 8 enzymatic loci revealed fixed differences in 2 diagnostic loci, adenylate kinase (Ak) and hexokinase (Hk), between sympatric and allopatric populations at 4 localities in Venezuela. The absence of heterozygotes for these 2 loci within 1 locality indicates, for the first time, the presence of 2 sympatric reproductively isolated populations or cryptic species within L. longipalpis. Significant differences were also detected between these cryptic species in the allele frequencies of glucose-6-phosphate isomerase (Gpi) and malate dehydrogenase, decarboxylating (Me). One species showed mean heterozygosities that ranged between 6.6% and 6.7%, with 1.6-1.9 alleles detected per locus, while the other had mean heterozygosities that ranged from 4.3% to 6.3%, with 1.3-1.6 alleles per locus. Comparisons of isozyme profiles with published data suggests that 1 species is similar to the L. longipalpis described in Colombian and Brazilian populations, whereas the other has not been previously reported.

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The parasite Schistosoma mansoni lacks the de novo pathway for purine biosynthesis and depends on salvage pathways for its purine requirements. Schistosomiasis is endemic in 76 countries and territories and amongst the parasitic diseases ranks second after malaria in terms of social and economic impact and public health importance. The PNP is an attractive target for drug design and it has been submitted to extensive structure-based design. The atomic coordinates of the complex of human PNP with inosine were used as template for starting the modeling of PNP from S. mansoni complexed with inosine. Here we describe the model for the complex SmPNP-inosine and correlate the structure with differences in the affinity for inosine presented by human and S. mansoni PNPs. (C) 2004 Elsevier B.V. All rights reserved.

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Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine-salvage pathway, which allows cells to utilize preformed bases and nucleosides in order to synthesize nucleotides. PNP is specific for purine nucleosides in the beta-configuration and exhibits a strong preference for purines containing a 6-keto group and ribosyl-containing nucleosides relative to the corresponding analogues. PNP was crystallized in complex with ligands and data collection was performed using synchrotron radiation. This work reports the structure of human PNP in complex with guanosine (at 2.80 angstrom resolution), 3' deoxyguanosine (at 2.86 angstrom resolution) and 8-azaguanine (at 2.85 angstrom resolution). These structures were compared with the PNP-guanine, PNP-inosine and PNP-immucillin-H complexes solved previously.