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Cloning of a guanosine-inosine kinase gene of Escherichia coli and characterization of the purified gene product.

Mori, H; Iida, A; Teshiba, S; Fujio, T
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1995 EN
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27.41%
We attempted to clone an inosine kinase gene of Escherichia coli. A mutant strain which grows slowly with inosine as the sole purine source was used as a host for cloning. A cloned 2.8-kbp DNA fragment can accelerate the growth of the mutant with inosine. The fragment was sequenced, and one protein of 434 amino acids long was found. This protein was overexpressed. The overexpressed protein was purified and characterized. The enzyme had both inosine and guanosine kinase activity. The Vmaxs for guanosine and inosine were 2.9 and 4.9 mumol/min/mg of protein, respectively. The Kms for guanosine and inosine were 6.1 microM and 2.1 mM, respectively. This enzyme accepted ATP and dATP as a phosphate donor but not p-nitrophenyl phosphate. These results show clearly that this enzyme is not a phosphotransferase but a guanosine kinase having low (Vmax/Km) activity with inosine. The sequence of the gene we have cloned is almost identical to that of the gsk gene (K.W. Harlow, P. Nygaard, and B. Hove-Jensen, J. Bacteriol. 177:2236-2240, 1995).

Production of Nucleic Acid-Related Substances by Fermentation Processes: XXXIII. Accumulation of Inosine by a Mutant of Brevibacterium ammoniagenes

Furuya, Akira; Abe, Shigeo; Kinoshita, Shukuo
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1970 EN
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27.44%
Inosine-producing cultures were found among mutants resistant to 6-mercaptoguanine (6MG) derived from a 5′-inosinic acid (IMP)-producing strain, KY 13102, of Brevibacterium ammoniagenes. Inosine-producing ability was very frequent among the mutants resistant to a low concentration (10 to 50 μg/ml) of 6MG. The accumulation of inosine by strain KY 13714 was stimulated by a low concentration of adenine (25 mg/liter) but was depressed by high levels of adenine. The accumulation by strain KY 13714 was not inhibited by manganese ion but instead was stimulated by its excess, in contrast to IMP accumulation by KY 13102. Addition of hypoxanthine at an early stage of cultivation accelerated inosine accumulation. Furthermore, on addition of hypoxanthine and of a surface-activating agent after 48 hr of cultivation, the simultaneous accumulation of IMP and inosine was observed. A 9.3-mg amount of inosine per ml accumulated after 4 days of cultivation at 30 C. The inosine-producing mutant did not differ from the IMP-producing strain either in 5′ purine nucleotide degradation or in IMP formation from hypoxanthine. However, it was found to be completely devoid of purine nucleoside-degrading activity. The conversion of IMP accumulation to inosine can be explained by the lack of nucleosidedegrading activity. The relationship between deficiency of nucleoside-degrading activity and resistance to low levels of 6MG is discussed...

Interaction of metabolism of aspartate and inosine and energy state of malignant cells.

Kovacević, Z; Popović, J; Brkljac, O; Lelas, S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/10/1987 EN
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1. Oxidation of glutamine in Ehrlich ascites-carcinoma cells results in a large accumulation of aspartate. 2.The addition of inosine causes a marked decrease in aspartate production from glutamine. This may be related to the resynthesis of AMP from aspartate and IMP, the latter being produced from inosine via the salvage pathway for purine nucleotides. In accordance with this assumption, a significant production of lactate was observed, which comes probably from the ribose moiety of inosine. Since lactate is known to inhibit production of aspartate from glutamine, this may explain the effect of inosine. 3. Addition of glutamine together with inosine increased cellular ATP content. This was not the case if glutamine or inosine was present separately or if inosine was added together with lactate, pyruvate or glucose. The effect did not occur if amino-oxyacetate, an inhibitor of transaminases, was added. These findings suggested again that production of aspartate is important for resynthesis of ATP from IMP via the purine nucleotide cycle. 4.If the cells were exposed to prolonged anaerobic incubation, addition of glutamine and inosine markedly increased O2 uptake and [ATP], suggesting the crucial importance of aspartate production by glutamine oxidation for the recovery of energy metabolism in the cells.

Inosine-stimulated insulin release and metabolism of inosine in isolated mouse pancreatic islets.

Capito, K; Hedeskov, C J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/08/1976 EN
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27.52%
Inosine is a potent primary stimulus of insulin secretion from isolated mouse islets. The inosine-induced insulin secretion was totally depressed during starvation, but was completely restored by the addition of 5 mM-caffeine to the medium and partially restored by the addition of 5 mM-glucose. Mannoheptulose (3 mg/ml) potentiated the effect of 10 mM-inosine in islets from fed mice. The mechanism of the stimulatory effect of inosine was further investigated, and it was demonstrated that pancreatic islets contain a nucleoside phosphorylase capable of converting inosine into hypoxanthine and ribose 1-phosphate. Inosine at 10 mM concentration increased the lactate production and the content of ATP, glucose 6-phosphate (fructose 1,6-diphosphate + triose phosphates) and cyclic AMP in islets from fed mice. In islets from starved mice inosine-induced lactate production was decreased and no change in the concentration of cyclic AMP could be demonstrated, whereas the concentration of ATP and glucose 6-phosphate rose. Inosine (10 mM) induced a higher concentration of (fructose 1,6-diphosphate + triose phosphates) in islets from starved mice than in islets from fed mice suggesting that in starvation the activities of glyceraldehyde 3-phosphate dehydrogenase or other enzymes below this step in glycolysis are decreased. Formation of glucose from inosine was negligible. Inosine had no direct effect on adenylate cyclase activity in islet homogenates. The observed changes in insulin secretion and islet metabolism mimic what is seen when glucose and glyceraldehyde stimulate insulin secretion...

The release of adenosine and inosine from canine subcutaneous adipose tissue by nerve stimulation and noradrenaline.

Fredholm, B B; Sollevi, A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //1981 EN
Relevância na Pesquisa
27.36%
1. Plasma and adipose tissue purine nucleosides were assayed by reversed phase high-performance liquid chromatography after purification of the samples on phenylboronate affinity gel. 2. The adenosine content of unstimulated subcutaneous adipose tissue was close to 1 n-mole/g. The concentrations of adenosine and inosine in canine arterial plasma were 0.26 +/- 0.03 and 0.16 +/- 0.03 microM, respectively. In venous plasma from the canine subcutaneous adipose tissue the corresponding values were 0.32 +/- 0.04 and 0.28 +/- 0.06 microM under basal conditions. The arterio-venous concentration difference of adenosine was linearly dependent upon the arterial adenosine concentration. At arterial concentrations below 0.3 microM there was a net production of adenosine; above 0.3 microM there was a net extraction of approximately 77% of the adenosine. Adenosine was extensively eliminated in blood. The major part of this elimination could be accounted for by metabolism to inosine, hypoxanthine and uric acid. 3. Following sympathetic nerve stimulation (4 Hz for 20 min) the rate of adenosine outflow from adipose tissue increased from 0.33 +/- 0.22 to a peak value of 1.2 +/- 0.26 n-mole/min. This corresponds to a net release of 8.7 +/- 3.0 n-mole/100 g tissue. Inosine outflow rose from 0.64 +/- 0.37 to 5.3 +/- 1.4 n-mole/min...

Inosine Protects Against the Development of Diabetes in Multiple-Low-Dose Streptozotocin and Nonobese Diabetic Mouse Models of Type 1 Diabetes

Mabley, Jon G; Rabinovitch, Alex; Suarez-Pinzon, Wilma; Haskó, György; Pacher, Pál; Power, Robert; Southan, Gary; Salzman, Andrew; Szabó, Csaba
Fonte: ScholarOne Publicador: ScholarOne
Tipo: Artigo de Revista Científica
Publicado em //2003 EN
Relevância na Pesquisa
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Inosine, a naturally occurring purine, was long considered to be an inactive metabolite of adenosine. However, recently inosine has been shown to be an immunomodulator and anti-inflammatory agent. The aim of this study was to determine whether inosine influences anti-inflammatory effects and affects the development of type 1 diabetes in murine models. Type 1 diabetes was induced either chemically by streptozotocin or genetically using the nonobese diabetic mouse (NOD) model. Mice were treated with inosine (100 or 200 mg kg−1d−1) and diabetes incidence was monitored. The effect of inosine on pancreas immune cell infiltration, oxidative stress, and cytokine profile also was determined. For the transplantation model islets were placed under the renal capsule of NOD mice and inosine (200 mg kg−1d−1) treatment started the day of islet transplantation. Graft rejection was diagnosed by return of hyperglycemia accompanied by glucosuria and ketonuria. Inosine reduced the incidence of diabetes in both streptozotocin-induced diabetes and spontaneous diabetes in NOD mice. Inosine decreased pancreatic leukocyte infiltration and oxidative stress in addition to switching the cytokine profile from a Th1 to a Th2 profile. Inosine prolonged pancreatic islet graft survival...

The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes

Mabley, Jon G; Pacher, Pal; Murthy, Kanneganti G K; Williams, William; Southan, Garry J; Salzman, Andrew L; Szabo, Csaba
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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Endogenous purines including inosine have been shown to exert immunomodulatory and anti-inflammatory effects in a variety of disease models. The dosage of inosine required for protection is very high because of the rapid metabolism of inosine in vivo. The aim of this study was to determine whether a metabolic-resistant purine analogue, INO-2002, exerts anti-inflammatory effects in two animal models of type I diabetes. Type I diabetes was induced chemically with streptozotocin or genetically using the non-obese diabetic (NOD) female mouse model. Mice were treated with INO-2002 or inosine as required at 30, 100, or 200 mg/kg per day, while blood glucose and diabetes incidence were monitored. The effect of INO-2002 on the pancreatic cytokine profile was also determined. INO-2002 reduced both the hyperglycaemia and incidence of diabetes in both streptozotocin-induced and spontaneous diabetes in NOD mice. INO-2002 proved to be more effective in protecting against diabetes than the naturally occurring purine, inosine, when administered at the same dose. INO-2002 treatment decreased pancreatic levels of interleukin (IL)-12 and tumour necrosis factor-α, while increasing levels of IL-4 and IL-10. INO-2002 also reduced pancreatic levels of the chemokine MIP-1α. The inosine analogue...

Inosine Alters Gene Expression and Axonal Projections in Neurons Contralateral to a Cortical Infarct and Improves Skilled Use of the Impaired Limb

Zai, Laila; Ferrari, Christina; Subbaiah, Sathish; Havton, Leif A.; Coppola, Giovanni; Strittmatter, Stephen; Irwin, Nina; Geschwind, Daniel; Benowitz, Larry I.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 24/06/2009 EN
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Recovery after stroke and other types of brain injury is restricted in part by the limited ability of undamaged neurons to form compensatory connections. Inosine, a naturally occurring purine nucleoside, stimulates neurons to extend axons in culture and, in vivo, enhances the ability of undamaged neurons to form axon collaterals after brain damage. The molecular changes induced by inosine are unknown, as is the ability of inosine to restore complex functions associated with a specific cortical area. Using a unilateral injury model limited to the sensorimotor cortex, we show that inosine triples the number of corticospinal tract axons that project from the unaffected hemisphere and form synaptic bouton-like structures in the denervated half of the spinal cord. These changes correlate with improved recovery in animals’ ability to grasp and consume food pellets with the affected forepaw. Studies using laser-capture microdissection and microarray analysis show that inosine profoundly affects gene expression in corticospinal neurons contralateral to the injury. Inosine attenuates transcriptional changes caused by the stroke, while upregulating the expression of genes associated with axon growth and the complement cascade. Thus, inosine alters gene expression in neurons contralateral to a stroke...

Inosine augments the effects of a Nogo receptor blocker and of environmental enrichment to restore skilled forelimb use after stroke

Zai, Laila; Ferrari, Christina; Dice, Carlie; Subbaiah, Sathish; Havton, Leif A.; Coppola, Giovanni; Geschwind, Daniel; Irwin, Nina; Huebner, Eric; Strittmatter, Stephen M.; Benowitz, Larry I.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 20/04/2011 EN
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Stroke is the leading cause of disability in much of the world, with few treatment options available. Following unilateral stroke in rats, inosine, a naturally occurring purine nucleoside, stimulates the growth of projections from the undamaged hemisphere into denervated areas of the spinal cord and improves skilled use of the impaired forelimb. Inosine augments neurons’ intrinsic growth potential by activating Mst3b, a component of the signal-transduction pathway through which trophic factors regulate axon outgrowth. The present study investigated whether inosine would complement the effects of treatments that promote plasticity through other mechanisms. Following unilateral stroke in the rat forelimb motor area, inosine combined with NEP1-40, a Nogo receptor antagonist, doubled the number of axon branches extending from neurons in the intact hemisphere into the denervated side of the spinal cord compared to either treatment alone and restored rats’ level of skilled reaching using the impaired forepaw to preoperative levels. Similar functional improvements were seen when inosine was combined with environmental enrichment (EE). The latter effect was associated with changes in gene expression in layer 5 pyramidal neurons of the undamaged cortex well beyond those seen with inosine or EE alone. Inosine is now in clinical trials for other indications...

The Pentose Moiety of Adenosine and Inosine Is an Important Energy Source for the Fermented-Meat Starter Culture Lactobacillus sakei CTC 494▿

Rimaux, T.; Vrancken, G.; Vuylsteke, B.; De Vuyst, L.; Leroy, F.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/2011 EN
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The genome sequence of Lactobacillus sakei 23K has revealed that the species L. sakei harbors several genes involved in the catabolism of energy sources other than glucose in meat, such as glycerol, arginine, and nucleosides. In this study, a screening of 15 L. sakei strains revealed that arginine, inosine, and adenosine could be used as energy sources by all strains. However, no glycerol catabolism occurred in any of the L. sakei strains tested. A detailed kinetic analysis of inosine and adenosine catabolism in the presence of arginine by L. sakei CTC 494, a fermented-meat starter culture, was performed. It showed that nucleoside catabolism occurred as a mixed-acid fermentation in a pH range (pH 5.0 to 6.5) relevant for sausage fermentation. This resulted in the production of a mixture of acetic acid, formic acid, and ethanol from ribose, while the nucleobase (hypoxanthine and adenine in the case of fermentations with inosine and adenosine, respectively) was excreted into the medium stoichiometrically. This indicates that adenosine deaminase activity did not take place. The ratios of the different fermentation end products did not vary with environmental pH, except for the fermentation with inosine at pH 5.0, where lactic acid was produced too. In all cases...

Anti-inflammatory effects of purine nucleosides, adenosine and inosine, in a mouse model of pleurisy: evidence for the role of adenosine A2 receptors

da Rocha Lapa, Fernanda; da Silva, Morgana Duarte; de Almeida Cabrini, Daniela; Santos, Adair R. S.
Fonte: Springer Netherlands Publicador: Springer Netherlands
Tipo: Artigo de Revista Científica
EN
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Adenosine and its metabolite, inosine, have been described as molecules that participate in regulation of inflammatory response. The aim of this study was to investigate the effect of adenosine and inosine in a mouse model of carrageenan-induced pleurisy as well as the participation of adenosine receptors in this response. Injection of carrageenan into the pleural cavity induced an acute inflammatory response characterized by leukocyte migration, pleural exudation, and increased release of interleukin-1β and tumor necrosis factor-α in pleural exudates. The treatment with adenosine (0.3–100 mg/kg, i.p.) and inosine (0.1–300 mg/kg, i.p.) 30 min before carrageenan injection reduced significantly all these parameters analyzed. Our results also demonstrated that A2A and A2B receptors seem to mediate the adenosine and inosine effects observed, since pretreatment with selective antagonists of adenosine A2A (ZM241385) and A2B (alloxazine) receptors, reverted the inhibitory effects of adenosine and inosine in pleural inflammation. The involvement of A2 receptors was reinforced with adenosine receptor agonist CGS21680 treatment, since its anti-inflammatory effects were reversed completely and partially with ZM241385 and alloxazine injection...

Role of pertussis toxin-sensitive G-protein, K+ channels, and voltage-gated Ca2+ channels in the antinociceptive effect of inosine

Macedo-Junior, Sérgio José; Nascimento, Francisney Pinto; Luiz-Cerutti, Murilo; Santos, Adair Roberto Soares
Fonte: Springer Netherlands Publicador: Springer Netherlands
Tipo: Artigo de Revista Científica
EN
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Inosine is the first metabolite of adenosine. It exerts an antinociceptive effect by activating the adenosine A1 and A2A receptors. We have previously demonstrated that inosine exhibits antinociceptive properties in acute and chronic mice models of nociception. The aim of this study was to investigate the involvement of pertussis toxin-sensitive G-protein-coupled receptors, as well as K+ and Ca2+ channels, in the antinociception promoted by inosine in the formalin test. Mice were pretreated with pertussis toxin (2.5 μg/site, i.t., an inactivator of Gi/0 protein); after 7 days, they received inosine (10 mg/kg, i.p.) or morphine (2.5 mg/kg, s.c., used as positive control) immediately before the formalin test. Another group of animals received tetraethylammonium (TEA) or 4-aminopyridine (4-AP) (1 μg/site, i.t., a non-specific voltage-gated K+ channel blockers), apamin (50 ng/site, i.t., a small conductance Ca2+-activated K+ channel blocker), charybdotoxin (250 pg/site, i.t., a large-conductance Ca2+-activated K+ channel blocker), glibenclamide (100 μg/site, i.t., an ATP-sensitive K+ channel blocker) or CaCl2 (200 nmol/site, i.t.). Afterwards, the mice received inosine (10 mg/kg, i.p.), diclofenac (10 mg/kg, i.p., a positive control)...

The antidepressant-like effect of inosine in the FST is associated with both adenosine A1 and A2A receptors

Kaster, Manuella P.; Budni, Josiane; Gazal, Marta; Cunha, Mauricio P.; Santos, Adair R. S.; Rodrigues, Ana Lúcia S.
Fonte: Springer Netherlands Publicador: Springer Netherlands
Tipo: Artigo de Revista Científica
EN
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Inosine is an endogenous purine nucleoside, which is formed during the breakdown of adenosine. The adenosinergic system was already described as capable of modulating mood in preclinical models; we now explored the effects of inosine in two predictive models of depression: the forced swim test (FST) and tail suspension test (TST). Mice treated with inosine displayed higher anti-immobility in the FST (5 and 50 mg/kg, intraperitoneal route (i.p.)) and in the TST (1 and 10 mg/kg, i.p.) when compared to vehicle-treated groups. These antidepressant-like effects started 30 min and lasted for 2 h after intraperitoneal administration of inosine and were not accompanied by any changes in the ambulatory activity in the open-field test. Both adenosine A1 and A2A receptor antagonists prevented the antidepressant-like effect of inosine in the FST. In addition, the administration of an adenosine deaminase inhibitor (1 and 10 mg/kg, i.p.) also caused an antidepressant-like effect in the FST. These results indicate that inosine possesses an antidepressant-like effect in the FST and TST probably through the activation of adenosine A1 and A2A receptors, further reinforcing the potential of targeting the purinergic system to the management of mood disorders.

Anti-inflammatory effects of inosine in allergic lung inflammation in mice: evidence for the participation of adenosine A2A and A3 receptors

da Rocha Lapa, Fernanda; de Oliveira, Ana Paula Ligeiro; Accetturi, Beatriz Golega; de Oliveira Martins, Isabelli; Domingos, Helory Vanni; de Almeida Cabrini, Daniela; de Lima, Wothan Tavares; Santos, Adair Roberto Soares
Fonte: Springer Netherlands Publicador: Springer Netherlands
Tipo: Artigo de Revista Científica
EN
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27.53%
Inosine, a naturally occurring purine formed from the breakdown of adenosine, is associated with immunoregulatory effects. Evidence shows that inosine modulates lung inflammation and regulates cytokine generation. However, its role in controlling allergen-induced lung inflammation has yet to be identified. In this study, we aimed to investigate the role of inosine and adenosine receptors in a murine model of lung allergy induced by ovalbumin (OVA). Intraperitoneal administration of inosine (0.001–10 mg/kg, 30 min before OVA challenge) significantly reduced the number of leukocytes, macrophages, lymphocytes and eosinophils recovered in the bronchoalveolar lavage fluid of sensitized mice compared with controls. Interestingly, our results showed that pre-treatment with the selective A2A receptor antagonist (ZM241385), but not with the selective A2B receptor antagonist (alloxazine), reduced the inhibitory effects of inosine against macrophage count, suggesting that A2A receptors mediate monocyte recruitment into the lungs. In addition, the pre-treatment of mice with selective A3 antagonist (MRS3777) also prevented inosine effects against macrophages, lymphocytes and eosinophils. Histological analysis confirmed the effects of inosine and A2A adenosine receptors on cell recruitment and demonstrated that the treatment with ZM241385 and alloxazine reverted inosine effects against mast cell migration into the lungs. Accordingly...

Inosine Enhances Axon Sprouting and Motor Recovery after Spinal Cord Injury

Kim, Daniel; Zai, Laila; Liang, Peng; Schaffling, Colleen; Ahlborn, David; Benowitz, Larry I.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 02/12/2013 EN
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27.36%
Although corticospinal tract axons cannot regenerate long distances after spinal cord injury, they are able to sprout collateral branches rostral to an injury site that can help form compensatory circuits in cases of incomplete lesions. We show here that inosine enhances the formation of compensatory circuits after a dorsal hemisection of the thoracic spinal cord in mature rats and improves coordinated limb use. Inosine is a naturally occurring metabolite of adenosine that crosses the cell membrane and, in neurons, activates Mst3b, a protein kinase that is part of a signal transduction pathway that regulates axon outgrowth. Compared to saline-treated controls, rats with dorsal hemisections that were treated with inosine showed three times as many synaptic contacts between corticospinal tract collaterals and long propriospinal interneurons that project from the cervical cord to the lumbar level. Inosine-treated rats also showed stronger serotonergic reinnervation of the lumbar cord than saline-treated controls, and performed well above controls in both open-field testing and a horizontal ladder rung-walking test. Inosine was equally effective whether delivered intracranially or intravenously, and has been shown to be safe for other indications in humans. Thus...

Adenosine and inosine exert cytoprotective effects in an in vitro model of liver ischemia-reperfusion injury

MÓDIS, KATALIN; GERŐ, DOMOKOS; STANGL, RITA; ROSERO, OLIVÉR; SZIJÁRTÓ, ATTILA; LOTZ, GÁBOR; MOHÁCSIK, PETRA; SZOLECZKY, PETRA; COLETTA, CIRO; SZABÓ, CSABA
Fonte: D.A. Spandidos Publicador: D.A. Spandidos
Tipo: Artigo de Revista Científica
EN
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Liver ischemia represents a common clinical problem. In the present study, using an in vitro model of hepatic ischemia-reperfusion injury, we evaluated the potential cytoprotective effect of the purine metabolites, such as adenosine and inosine, and studied the mode of their pharmacological actions. The human hepatocellular carcinoma-derived cell line HepG2 was subjected to combined oxygen-glucose deprivation (COGD; 0-14-24 h), followed by re-oxygenation (0-4-24 h). Adenosine or inosine (300–1,000 μM) were applied in pretreatment. Cell viability and cytotoxicity were measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and lactate dehydrogenase methods, respectively. The results showed that both adenosine and inosine exerted cytoprotective effects, and these effects were not related to receptor-mediated actions, since they were not prevented by selective adenosine receptor antagonists. On the other hand, the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA, 10 μM) markedly and almost fully reversed the protective effect of adenosine during COGD, while it did not influence the cytoprotective effect of inosine in the same assay conditions. These results suggest that the cytoprotective effects are related to intracellular actions...

Voltammetric and impedance studies of inosine-5'-monophosphate and hypoxanthine

Oliveira-Brett, Ana Maria; Silva, Luís A.; Farace, Giosi; Vadgama, Pankaj; Brett, Christopher M. A.
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica Formato: aplication/PDF
ENG
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The oxidation mechanism and adsorption of inosine 5'-monophosphate and hypoxanthine were investigated in solutions of different pH using voltammetric and impedance methods at glassy carbon electrodes. For both compounds, the pH dependence from differential pulse voltammetry showed that the same number of electrons and protons are involved in the rate-determining step of the electrochemical reaction. In the case of hypoxanthine, it was also possible to study the effect of different concentrations. At high concentrations of hypoxanthine, two oxidation peaks were observed, the first due to hypoxanthine oxidation with formation of oligomers and the second due to hypoxanthine oligomer oxidation, both compounds adsorbing strongly. Impedance measurements corroborated the voltammetric results and enabled the study of the adsorption of hypoxanthine on glassy carbon.; http://www.sciencedirect.com/science/article/B6W72-47R9YPB-1/1/a6995627364cc875adcae0c8f04fbcd5

Inosine-Mediated Modulation of RNA Sensing by Toll-Like Receptor 7 (TLR7) and TLR8

Sarvestani, Soroush T.; Tate, Michelle D.; Moffat, Jessica M.; Jacobi, Ashley M.; Behlke, Mark A.; Miller, Alistair R.; Beckham, Simone A.; McCoy, Claire E.; Chen, Weisan; Mintern, Justine D.; O'Keeffe, Meredith; John, Matthias; Williams, Bryan R. G.; Gan
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /01/2014 EN
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RNA-specific adenosine deaminase (ADAR)-mediated adenosine-to-inosine (A-to-I) editing is a critical arm of the antiviral response. However, mechanistic insights into how A-to-I RNA editing affects viral infection are lacking. We posited that inosine incorporation into RNA facilitates sensing of nonself RNA by innate immune sensors and accordingly investigated the impact of inosine-modified RNA on Toll-like receptor 7 and 8 (TLR7/8) sensing. Inosine incorporation into synthetic single-stranded RNA (ssRNA) potentiated tumor necrosis factor alpha (TNF-α) or alpha interferon (IFN-α) production in human peripheral blood mononuclear cells (PBMCs) in a sequence-dependent manner, indicative of TLR7/8 recruitment. The effect of inosine incorporation on TLR7/8 sensing was restricted to immunostimulatory ssRNAs and was not seen with inosine-containing short double-stranded RNAs or with a deoxy-inosine-modified ssRNA. Inosine-mediated increase of self-secondary structure of an ssRNA resulted in potentiated IFN-α production in human PBMCs through TLR7 recruitment, as established through the use of a TLR7 antagonist and Tlr7-deficient cells. There was a correlation between hyperediting of influenza A viral ssRNA and its ability to stimulate TNF-α...

The 3' terminal sequence of the inosine monophosphate dehydrogenase gene encodes an active domain in the yeast Schizosaccharomyces pombe

Karaer,Semian; Sarikaya,Aysegül Topal; Arda,Nazli; Temizkan,Güler
Fonte: Sociedade Brasileira de Genética Publicador: Sociedade Brasileira de Genética
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2006 EN
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The gua1 gene encoding inosine monophosphate dehydrogenase (IMPDH), which catalyses the first step in de novo biosynthesis of guanosine monophosphate (GMP), was cloned in the yeast Schizosaccharomyces pombe by functional complementation of a gua1ura4-D18 mutant strain from a S. pombe DNA genomic library. Complementation analysis revealed a 1.2 kb fragment which segregation analysis confirmed did not code for a suppressor gene. Only 446 nucleotides of the gua1 gene encoding the IMPDH C-terminal residues were found within this 1.2 kb sequence (GenBank, AJ293460). The comparison of this wild-type fragment with the same fragment from the gua1ura4-D18 mutant revealed that there was a point mutation at position 1261 (guanine -> adenine) from the 5' end, corresponding to the amino acid residue 421 (glycine -> serine) of the enzyme. Dot and Northern analyses showed that the gua1 gene was expressed in transformants as well as in the wild-type and the gua1ura4-D18 mutant, but enzyme activity was only detected in wild-type and transformant cells. It seems likely that a 446 bp fragment from the 3' end of the gua1 gene abolished the point mutation in the mutant strain, suggesting that this fragment participates in the sequences encoding the active domain of IMPDH in S. pombe.

Antiarrhythmic and arrhythmogenic action of inosine in experimental ventricular tachyarrhythmias

de Micheli,Alfredo; Pastelín,Gustavo; Chávez Domínguez,Rafael; Iturralde Torres,Pedro; Medrano,Gustavo A
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2009 EN
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Objective: To study the possible action of inosine on experimental ventricular tachyarrhythmias. Material and methods: We used 92 mongrel dogs weighing 13 kg-17 kg, anesthetized with 30 mg/kg sodium pentobarbital applied intravenously. Myocardial lesions were induced by injecting 1ml-1.5 ml of 70% phenol in the free wall of the left ventricle. In 36 dogs, the ventricular arrhythmia (VT) was induced 30 min later with aconitine crystals inserted into the periphery of the damaged area; in 16, VT was due only to myocardial damage and in the other 13 VT was spontaneously originated. Twenty-nine animals constituted the control group; no inosine was administered to them. The possible effects of inosine were studied in 63 animals. Leads II, aVR or aVL, right and left unipolar intraventricular leads and that on the wall of the superior vena cava were recorded under control conditions, once the myocardial damage had been induced, during the ventricular tachycardia, and following the injection of inosine. Of the 63 inosine-treated animals; in 34, VT was due to aconitine; in 16, it was produced only by the myocardial damage and, in 13, VT was presented spontaneously. Results: Sinus rhythm was not reestablished in the animals of the control group. Inosine reestablished the sinus rhythm in 26 of 34 dogs (76%) that received phenol and aconitine...