Navegando por Palavras-chave "NADPH oxidase"
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- ItemAcesso aberto (Open Access)Doença granulomatosa crônica autossômica: relato de caso e análise genético-molecular de dois irmãos brasileiros(Sociedade Brasileira de Pediatria, 2004-01-01) Prando-Andrade, Carolina; Agudelo-Florez, Piedad; Lopez, Juan A.; Paiva, Maria Aparecida de Souza; Costa-Carvalho, Beatriz Tavares [UNIFESP]; Condino-Neto, Antonio; Universidade Estadual de Campinas (UNICAMP); Hospital dos Servidores do Estado do Rio de Janeiro Setor de Pneumologia Pediátrica; Universidade Federal de São Paulo (UNIFESP)OBJECTIVE: To report the case of two siblings with chronic granulomatous disease. Chronic granulomatous disease is a primary immunodeficiency disorder characterized by abnormal microbicidal activity. Mutations in the p47-phox gene (NCF-1) are present in about 30% of the patients with chronic granulomatous disease; this group presents a better prognosis and later onset of recurrent infections as compared with the X-linked variant, present in about 56% of patients. DESCRIPTION: Case 1 is a female presenting repeat infections since age 10, starting with impetigo followed by severe pneumonia six months later. The severity of the lung infection associated with liver abscess and the patient's resistance to treatment prompted laboratory investigation for immunodeficiency. The results of the nitroblue tetrazolium and superoxide release tests were consistent with a diagnosis of chronic granulomatous disease. The parents and siblings were assessed, revealing the presence of granulomatous disease in a brother (Case 2). He also presented repeat infections with impetigo at age 10, followed by pneumonia six months later, however in a non severe form. Single-strand conformational polymorphism analysis detected abnormal electrophoretic mobility of exon 2 of the NCF-1 gene. Sequence DNA analysis revealed a dinucleotide GT deletion in exon 2. COMMENTS: It is important to evaluate the relatives of chronic granulomatous disease patients, even in the absence of typical clinical signs. Defining the mutation and its correlation with phenotype is important to provide appropriate genetic counseling and clinical prognosis.
- ItemSomente MetadadadosEffects of BAY 41-2272, an activator of nitric oxide-independent site of soluble guanylate cyclase, on human NADPH oxidase system from THP-1 cells(Elsevier B.V., 2007-07-12) Oliveira-Junior, Edgar Borges de; Thomazzi, Sara Maria; Relider, Jussara; Antunes, Edson; Condino-Neto, Antonio; Universidade Federal de São Paulo (UNIFESP); Univ Fed Sergipe; Universidade Estadual de Campinas (UNICAMP); Universidade de São Paulo (USP)We investigated the effects of the 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b] pyridin-3-yl]-pyrimidin-4-ylamine (BAY 41-2272) on the NADPH oxidase activity, gp91(phox) gene expression, cyclic guanosine-3',5-monophosphate (cGMP) and cyclic adenosine-3',5'-monophosphate (cAMP) levels in the human myelomonocytic THP-1 cell line. THP-1 cells treated with BAY 41-2272 (0.3-10 mu M) for 48 h significantly increased the superoxide anion (O-2(center dot-)) release. This increase was not affected when cells were pre-treated with the specific cGMP-phosphodiesterase inhibitor zaprinast, the soluble guanylate cyclase inhibitor 1H-[1,2,4] oxidiazolo[4,3-alpha] quinoxalin-1-one (ODQ), the adenylate cyclase inhibitor 9-(tetrahydro-2-furanyl) adenine (SQ 22,536) or the nitric oxide synthase inhibitor N-omega-nitro-1-arginine methyl ester (I-NAME). in addition, BAY 41-2272 (3 and 10 mu M; 48 h) was able to increase gp91(phox) gene expression on THP-1 cells. the pre-treatment with zaprinast, 3-isobutyl-L-methyl-xanthine (IBMX; 0.5 mM), ODQ, SQ 22,536 or l-NAME caused no additional effect on the expression of gp91(phox) evoked by BAY 41-2272. Treatment of THP-1 cells with BAY 41-2272 caused a significant increase in cGMP and cAMP levels. Our findings show that BAY 41-2272 caused a significant increase on the O-2(center dot-) release and gp91(phox) gene expression by THP-1 cells, and an elevation of intracellular cGMP and cAMP levels. However, we could not detect a clear correlation between both O-2(center dot-) release and gp91(phox) gene expression with activation of cGMP and cAMP signaling pathways. (c) 2007 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosMelatonin modifies basal and stimulated insulin secretion via NADPH oxidase(Bioscientifica Ltd, 2016) Simoes, Daniel; Riva, Patricia; Peliciari-Garcia, Rodrigo Antonio [UNIFESP]; Cruzat, Vinicius Fernandes; Graciano, Maria Fernanda; Munhoz, Ana Claudia; Taneda, Marco; Cipolla-Neto, Jose; Carpinelli, Angelo RafaelMelatonin is a hormone synthesized in the pineal gland, which modulates several functions within the organism, including the synchronization of glucose metabolism and glucose-stimulated insulin secretion (GSIS). Melatonin can mediate different signaling pathways in pancreatic islets through two membrane receptors and via antioxidant or pro-oxidant enzymes modulation. NADPH oxidase (NOX) is a pro-oxidant enzyme responsible for the production of the reactive oxygen specie (ROS) superoxide, generated from molecular oxygen. In pancreatic islets, NOX-derived ROS can modulate glucose metabolism and regulate insulin secretion. Considering the roles of both melatonin and NOX in islets, the aim of this study was to evaluate the association of NOX and ROS production on glucose metabolism, basal and GSIS in pinealectomized rats (PINX) and in melatonin-treated isolated pancreatic islets. Our results showed that ROS content derived from NOX activity was increased in PINX at baseline (2.8 mM glucose), which was followed by a reduction in glucose metabolism and basal insulin secretion in this group. Under 16.7 mM glucose, an increase in both glucose metabolism and GSIS was observed in PINX islets, without changes in ROS content. In isolated pancreatic islets from control animals incubated with 2.8 mM glucose, melatonin treatment reduced ROS content, whereas in 16.7 mM glucose, melatonin reduced ROS and GSIS. In conclusion, our results demonstrate that both basal and stimulated insulin secretion can be regulated by melatonin through the maintenance of ROS homeostasis in pancreatic islets.
- ItemAcesso aberto (Open Access)Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension(Elsevier B.V., 2011-07-01) Montenegro, Marcelo Freitas; Amaral, Jefferson Henrich; Pinheiro, Lucas Cézar; Sakamoto, Eliana Kiyomi; Ferreira, Graziele C.; Reis, Rosana Inacio dos [UNIFESP]; Marcal, Diogo Machado de Oliveira; Pereira, Romaiana Picada; Tanus-Santos, Jose Eduardo; Universidade de São Paulo (USP); Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Sergipe (UFS)Dietary nitrite and nitrate are important sources of nitric oxide (NO). However, the use of nitrite as an antihypertensive drug may be limited by increased oxidative stress associated with hypertension. We evaluated the antihypertensive effects of sodium nitrite given in drinking water for 4 weeks in two-kidney one-clip (21(1 C) hypertensive rats and the effects induced by nitrite on NO bioavailability and oxidative stress. We found that, even under the increased oxidative stress conditions present in 2K1C hypertension, nitrite reduced systolic blood pressure in a dose-dependent manner. Whereas treatment with nitrite did not significantly change plasma nitrite concentrations in 2K1C rats, it increased plasma nitrate levels significantly. Surprisingly, nitrite treatment exerted antioxidant effects in both hypertensive and sham-normotensive control rats. A series of in vitro experiments was carried out to show that the antioxidant effects induced by nitrite do not involve direct antioxidant effects or xanthine oxidase activity inhibition. Conversely, nitrite decreased vascular NADPH oxidase activity. Taken together, our results show for the first time that nitrite has antihypertensive effects in 2K1C hypertensive rats, which may be due to its antioxidant properties resulting from vascular NADPH oxidase activity inhibition. (C) 2011 Elsevier Inc. All rights reserved.
- ItemSomente MetadadadosTestosterone Induces Vascular Smooth Muscle Cell Migration by NADPH Oxidase and c-Src-Dependent Pathways(Lippincott Williams & Wilkins, 2012-06-01) Chignalia, Andreia Z.; Schuldt, Elke Z.; Camargo, Livia L.; Montezano, Augusto C.; Callera, Glaucia E.; Laurindo, Francisco R.; Lopes, Lucia R.; Avellar, Maria Christina Werneck [UNIFESP]; Carvalho, Maria Helena C.; Fortes, Zuleica B.; Touyz, Rhian M.; Tostes, Rita C.; Universidade de São Paulo (USP); Univ Ottawa; Universidade Federal de São Paulo (UNIFESP)Testosterone has been implicated in vascular remodeling associated with hypertension. Molecular mechanisms underlying this are elusive, but oxidative stress may be important. We hypothesized that testosterone stimulates generation of reactive oxygen species (ROS) and migration of vascular smooth muscle cells (VSMCs), with enhanced effects in cells from spontaneously hypertensive rats (SHRs). the mechanisms (genomic and nongenomic) whereby testosterone induces ROS generation and the role of c-Src, a regulator of redox-sensitive migration, were determined. VSMCs from male Wistar-Kyoto rats and SHRs were stimulated with testosterone (10(-7) mol/L, 0-120 minutes). Testosterone increased ROS generation, assessed by dihydroethidium fluorescence and lucigenin-enhanced chemiluminescence (30 minutes [SHR] and 60 minutes [both strains]). Flutamide (androgen receptor antagonist) and actinomycin D (gene transcription inhibitor) diminished ROS production (60 minutes). Testosterone increased Nox1 and Nox4 mRNA levels and p47phox protein expression, determined by real-time PCR and immunoblotting, respectively. Flutamide, actinomycin D, and cycloheximide (protein synthesis inhibitor) diminished testosterone effects on p47phox. c-Src phosphorylation was observed at 30 minutes (SHR) and 120 minutes (Wistar-Kyoto rat). Testosterone-induced ROS generation was repressed by 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-day]pyrimidin-4-amine (c-Src inhibitor) in SHRs and reduced by apocynin (antioxidant/NADPH oxidase inhibitor) in both strains. Testosterone stimulated VSMCs migration, assessed by the wound healing technique, with greater effects in SHRs. Flutamide, apocynin, and 3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-day] pyrimidin-4-amine blocked testosterone-induced VSMCs migration in both strains. Our study demonstrates that testosterone induces VSMCs migration via NADPH oxidase-derived ROS and c-Src-dependent pathways by genomic and nongenomic mechanisms, which are differentially regulated in VSMCs from Wistar-Kyoto rats and SHRs. (Hypertension. 2012; 59: 1263-1271.). Online Data Supplement