635 resultados para eNOS uncoupling


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The circadian behavior associated with the 24 hours light-dark (LD) cycle (T24) is due to a circadian clock , which in mammals is located in the hypothalamic suprachiasmatic nucleus (SCN). Under experimental conditions in which rats are espoused to a symmetric LD 22h cycle (T22) the two SCN regions, ventrolateral (vl) and dorsomedial (dm), can be functionally isolated, suggesting that each region regulates distinct physiological and behavioral components. The vl region regulates the locomotor activity and slow wave sleep (SWS) rhythms, while the dm region assures the body temperature and paradoxical sleep (PS) rhythms regulation. This research aimed to deepen the knowledge on the functional properties of circadian rhythmicity, specifically about the internal desynchronization process, and its consequences to locomotor activity and body temperature rhythms as well as to the sleep-wake cycle pattern in rats. We applied infrared motion sensors, implanted body temperature sensors and a telemetry system to record electrocorticogram (ECoG) and electromyogram (EMG) in two rat groups. The control group under 24h period LD cycle (T24: 12hL-12hD) to the baseline record and the experimental group under 22h period LD cycle (T22: 11hL- 11hD), in which is known to occur the uncoupling process of the circadian locomotor activity rhythm where the animals show two distinct locomotor activity rhythms: one synchronized to the external LD cycle, and another expressed in free running course, with period greater than 24h. As a result of 22h cycles, characteristic locomotor activity moment appear, that are coincidence moments (T22C) and non coincidence moments (T22NC) which were the main focus or our study. Our results show an increase in locomotor activity, especially in coincidence moments, and the inversion of locomotor activity, body temperature, and sleep-wake cycle patterns in non coincidence moments. We can also observe the increase in SWS and decrease in PS, both in coincidence and non coincidence moments. Probably the increases in locomotor activity as a way to promote the coupling between circadian oscillators generate an increased homeostatic pressure and thus increase SWS, promoting the decreasing in PS

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The studied area is geologically located in the Northern Domain of the Borborema Province (Northeast Brazil), limited to the south by the Patos shear zone. Terranes of the Jaguaribeano system are dominant, flanked by the Piranhas (E and S sides) and Central Ceará (NE side) terranes. Its basement comprises gneiss -migmatite terrains of Paleoproterozoic to Archean age (2.6 to 1.9 Ga old), overprinted by neoproterozoic to cambrian tectonotherma l events. Narrow supracrustal belts ( schist belts) display a 1.6 to 1.8 Ga age, as shown by whole - rock Rb-Sr and zircon U-Pb and Pb/Pb dates in acid metavolcanics which dominate in the lower section of these sequences, and in coeval metaplutonics (granitic augen gneisses). From the stratigraphic point of view, three Staterian belts are recognized: 1. Orós Belt - made up by the Orós Group, subdivided in the Santarém (predominantly pure to impure quartzites, micaschists and metacarbonates) and Campo Alegre (metandesites, metabasalts, metarhyolites and metarhyodacites, interlayered with metatuffs and metasediments) formations, and by the Serra do Deserto Magmatic Suite (granitic augen gneisses). 2. Jaguaribe Belt - its lithostratigrahic-lithodemic framework is similar to the one of the Orós Belt, however with a greater expression of the volcano -plutonic components (Campo Alegre Formation and Serra do Deserto Magmatic Suite). The Peixe Gordo Sequence, separately described, is also related to this belt and contain s metasedimentary, metavolcanic (with subordinated volcanoclastics) and metaplutonic units. The first one correlated to the Orós Group and the latter the Serra do Deserto Magmatic Suite. 3. Western Potiguar Belt - represented by the Serra de São José Gro up, subdivided in the Catolezinho (biotite -amphibole gneisses with intercalations of metacarbonates, calcsilicate rocks, amphibolites and quartzite beds to the top) and Minhuins (quartzites, micaschists, metaconglomerates, calcsilicate rocks, acid to the b asic metavolcanics and metatuffs) formations. Its late Paleoproterozoic (Staterian) age was established by a Pb/Pb date on zircons from a granitic orthogneiss of the Catolezinho Formation. The petrographic characteristics and sedimentary structures of the Santarém Formation of the Orós Group point to deltaic to shallow marine depositional systems, overlain by deep water deposits (turbidites). The geodynamic setting of this region encompassed a large depositional basin, probably extending to the east of the Portalegre shear zone and west of the Senador Pompeu shear zone, with possible equivalents in the Jucurutu Formation of the Seridó Belt and in the Ceará Group of central Ceará. The Arneiróz Belt, west Ceará, displays some stratigraphic features and granito ids geochemically akin to the ones of the Orós Belt. The evolutionary setting started with an extensional phase which was more active in the eastern part of this domain (Western Potiguar and part of the Jaguaribe belts), where the rudite and psamite sedime ntation relates to a fluviatile rift environment which evolved to a prograding deltaic system to the west (Orós Group). The basaltic andesitic and rhyolitic volcanics were associated to this extensional phase. During this magmatic event, acid magmas also crystallized at plutonic depths. The Orós Group illustrates the environmental conditions in the western part of this domain. Later on, after a large time gap (1.6 to 1.1 Ga), the region was subjected to an extensional deformational episode marked by 900 Ma old (Sm-Nd data) basic rocks, possibly in connection with the deposition of the Cachoeirinha Group south of the Patos shear zone. In the 800 to 500 Ma age interval, the region was affected by important deformational and metamorphic events coupled with in trusion of granitic rocks of variable size (dykes to batholiths), related to the Brasiliano/Pan -African geotectonic cycle. These events produced structural blocks which differentiate, one from the other, according to the importance of anatectic mobilizatio n, proportion of high-grade supracrustals and the amount of neoproterozoic -cambrian granitoid intrusions. On this basis, a large portion of the Jaguaretama Block/Terrane is relatively well preserved from this late overprint. The border belts of the Jagua retama Block (Western Potiguar and Arneiroz) display kyanite-bearing (medium pressure) mineral associations, while in the inner part of the block there is a north-south metamorphic zoning marked by staurolite or sillimanite peak metamorphic conditions. Regarding the deformations of the Staterian supracrustal rocks, second and third phases were the most important, diagnosed as having developed in a progressive tectonic process. In the general, more vigorous conditions of PT are related to the interval tardi - phase 2 early-phase 3, whose radiometric ages and regional structuring indicators places it in the Brasiliano/Pan-African Cycle. In the Staterian geodynamic setting of Brazilian Platform , these sequences are correlated to the lower Espinhaço Supergroup (p.ex., Rio dos Remédios and Paraguaçu groups, a paleproterozoic rift system in the São Francisco Craton), the Araí and Serra da Mesa groups (north of Goiás, in the so -called Goiás Central Massif), and the Uatumã Group (in the Amazonian Craton). Granitic ( augen gneisses) plutonics are also known from these areas, as for example the A-type granites intrusive in the Araí and Serra da Mesa groups, dated at 1.77 Ga. Gravimetric and geological data place the limits of the Jaguaribeano System (terranes) along the Senador Pompeu Shear Zone (western border) and the Portalegre- Farias Brito shear zone (eastern and southern). However, the same data area not conclusive as regards the interpretation of those structures as suture of the terrane docking process. The main features of those shear zones and of involved lothological associations, appear to favour an intracontinental transpressional -transcurrent regime, during Neoproterozoic-Cambrian times, marking discontinuities along which different crustal blocks were laterally dispersed. Inside of this orogenic system and according to the magnetic data (total field map), the most important terrane boundary appears to be the Jaguaribe shear zone. The geochronological data, on some tectonostratigraphic associations (partly represented by the Ceará and Jucurutu groups), still at a preliminary level, besides the lack of granitic zonation and other petrotectonic criteria, do not allow to propose tectonic terrane assembly diagrams for the studied area

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In order to investigate a putative role for nitric oxide (NO) in the central nociceptive processing following carrageenan-induced arthritis in the rat temporomandibular joint (TMJ), we analyzed the immunoreactivity, gene expression and activity of nitric oxide synthases (NOS) in the caudal part of the spinal trigeminal nucleus (Sp5C) during the acute (24 h), chronic (15 days) and chronic-active (14 days-24 h) arthritis. In addition, evaluation of head-withdrawal threshold was carried out in all phases of arthritis under chronic inhibition of nNOS with the selective inhibitor 7-nitroindazole (7-NI). Neurons with nNOS-like immunoreactivity (nNOS-LI) were concentrated mainly in the lamina II of the Sp5C, showing no significant statistical difference during arthritis. Only a discrete percentage of nNOS-LI neurons expressed Fos immunoreactivity. The mRNA expression for both nNOS and endothelial nitric oxide synthases (eNOS) presented no noticeable differences among the groups. No expression of inducible nitric oxide synthase (iNOS) was detected in the Sp5C by either immunohistochemistry or reverse-transcription polymerase chain reaction (RTPCR). Ca(2+)-dependent NOS activity in the ipsilateral Sp5C was significantly higher (108.3 +/- 49.2%; P<0.01) in animals during the chronic arthritis. Interestingly, this increased activity was completely abolished 24 h later, in the chronic-active arthritis. Finally, head-withdrawal threshold decreased significantly in the chronic arthritis in animals under 7-NI chronic inhibition. In conclusion, nNOS immunoreactivity and mRNA expression are stable in the Sp5C during TMJ arthritis evolution, but its activity significantly increases in the chronic-phases supporting an antinociceptive role of the nNOS as evidenced by pain threshold experiment. (C) 2009 Elsevier B.V. All rights reserved.

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Increased replicative longevity in Saccharomyces cerevisiae because of calorie restriction has been linked to enhanced mitochondrial respiratory activity. Here we have further investigated how mitochondrial respiration affects yeast life span. We found that calorie restriction by growth in low glucose increased respiration but decreased mitochondrial reactive oxygen species production relative to oxygen consumption. Calorie restriction also enhanced chronological life span. The beneficial effects of calorie restriction on mitochondrial respiration, reactive oxygen species release, and replicative and chronological life span could be mimicked by uncoupling agents such as dinitrophenol. Conversely, chronological life span decreased in cells treated with antimycin (which strongly increases mitochondrial reactive oxygen species generation) or in yeast mutants null for mitochondrial superoxide dismutase (which removes superoxide radicals) and for RTG2 (which participates in retrograde feedback signaling between mitochondria and the nucleus). These results suggest that yeast aging is linked to changes in mitochondrial metabolism and oxidative stress and that mild mitochondrial uncoupling can increase both chronological and replicative life span.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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FUNDAMENTO: O polimorfismo T-786C do gene da sintetase do óxido nítrico endotelial (eNOS) e a produção de ânion superóxido podem diminuir a produção e biodisponibilidade do óxido nítrico, comprometendo o grau de vasodilatação, podendo este efeito ser revertido pelo exercício físico. OBJETIVO: Investigar a influência do treinamento aeróbico e do polimorfismo T-786C nas concentrações dos metabólitos do óxido nítrico (NOx), no fluxo sanguíneo (FS) e na pressão arterial (PA). MÉTODOS: Trinta e duas idosas pré-hipertensas (59 ± 6 anos) foram separadas em dois grupos de acordo com o polimorfismo T-786C (TT e TC+CC). Foram analisadas as concentrações de NOx (plasma) e fluxo sanguíneo por pletismografia de oclusão venosa em repouso, 1, 2 e 3 minutos pós-oclusão (FS-0, FS-1, FS-2, FS-3, respectivamente). As avaliações foram realizadas antes e após 6 meses de um programa de exercício aeróbico. RESULTADOS: Nas avaliações pré-treinamento, os níveis de NOx foram menores no grupo TC+CC em relação ao grupo TT. O grupo TT apresentou correlações entre NOx e FS-0 (r = 0,6) e pressão arterial diastólica (PAD) e FS-0 (r = -0,7), porém nenhuma correlação foi encontrada no grupo TC+CC. Nas avaliações pós-treinamento, ocorreram correlações entre NOx e FS-0 (r = 0,6) e nas mudanças do NOx e PAD (r = -0,6) no grupo TT. Também foram obtidas correlações entre PAD e FS-1 (r = -0,8), PAD e FS-2 (r = -0,6), PAD e FS-3 (r = -0,6), nas mudanças entre NOx e FS-1 (r = 0,8) e mudanças do NOx e PAD (r = -0,7) no grupo TC+CC. CONCLUSÃO: Conclui-se que 6 meses de exercício aeróbico podem contribuir para aumentar as relações existentes entre NO, PA e FS em idosas portadores do alelo C.

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

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Short-term cold exposure of homeothermic animals leads to higher thermogenesis and food consumption accompanied by weight loss. An analysis of cDNA-macroarray was employed to identify candidate mRNA species that encode proteins involved in thermogenic adaptation to cold. A cDNA-macroarray analysis, confirmed by RT-PCR, immunoblot, and RIA, revealed that the hypothalamic expression of melanin-concentrating hormone (MCH) is enhanced by exposure of rats to cold environment. The blockade of hypothalamic MCH expression by antisense MCH oligonucleotide in cold-exposed rats promoted no changes in feeding behavior and body temperature. However, MCH blockade led to a significant drop in body weight, which was accompanied by decreased liver glycogen, increased relative body fat, increased absolute and relative interscapular brown adipose tissue mass, increased uncoupling protein 1 expression in brown adipose tissue, and increased consumption of lean body mass. Thus, increased hypothalamic MCH expression in rats exposed to cold may participate in the process that allows for efficient use of energy for heat production during thermogenic adaptation to cold.

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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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Retinopathy, a common complication of diabetes, is characterized by an unbalanced production of nitric oxide (NO), a process regulated by nitric oxide synthase (NOS). We hypothesized that retinopathy might stem from changes in the insulin receptor substrate (IRS)/PI3K/AKT pathway and/or expression of NOS isoforms. Thus, we analysed the morphology and apoptosis index in retinas of obese rats in whom insulin resistance had been induced by a high-fat diet (HFD). Immunoblotting analysis revealed that the retinal tissue of HFD rats had lower levels of AKT1, eNOS and nNOS protein than those of samples taken from control animals. Furthermore, immunohistochemical analyses indicated higher levels of iNOS and 4-hydroxynonenal and a larger number of apoptotic nuclei in HFD rats. Finally, both the inner and outer retinal layers of HFD rats were thinner than those in their control counterparts. When considered alongside previous results, these patterns suggest two major ways in which HFD might impact animals: direct activity of ingested fatty acids and/or via insulin-resistance-induced changes in intracellular pathways. We discuss these possibilities in further detail and advocate the use of this animal model for further understanding relationships between retinopathy, metabolic syndrome and type 2 diabetes. © 2012 John Wiley & Sons, Ltd.

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Mammalian natriuretic peptides (NPs) have been extensively investigated for use as therapeutic agents in the treatment of cardiovascular diseases. Here, we describe the isolation, sequencing and tridimensional homology modeling of the first C-type natriuretic peptide isolated from scorpion venom. In addition, its effects on the renal function of rats and on the mRNA expression of natriuretic peptide receptors in the kidneys are delineated. Fractionation of Tityusserrulatus venom using chromatographic techniques yielded a peptide with a molecular mass of 2190.64Da, which exhibited the pattern of disulfide bridges that is characteristic of a C-type NP (TsNP, T. serrulatus Natriuretic Peptide). In the isolated perfused rat kidney assay, treatment with two concentrations of TsNP (0.03 and 0.1μg/mL) increased the perfusion pressure, glomerular filtration rate and urinary flow. After 60min of treatment at both concentrations, the percentages of sodium, potassium and chloride transport were decreased, and the urinary cGMP concentration was elevated. Natriuretic peptide receptor-A (NPR-A) mRNA expression was down regulated in the kidneys treated with both concentrations of TsNP, whereas NPR-B, NPR-C and CG-C mRNAs were up regulated at the 0.1μg/mL concentration. In conclusion, this work describes the isolation and modeling of the first natriuretic peptide isolated from scorpion venom. In addition, examinations of the renal actions of TsNP indicate that its effects may be related to the activation of NPR-B, NPR-C and GC-C. © 2013 Elsevier Ltd.

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