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Id: biblio-950745
Autor: Moreira, Priscila R; Maioli, Marcos A; Medeiros, Hyllana CD; Guelfi, Marieli; Pereira, Flávia TV; Mingatto, Fábio E.
Título: Protective effect of bixin on carbon tetrachloride-induced hepatotoxicity in rats
Fonte: Biol. Res;47:1-7, 2014. ilus, graf.
Idioma: en.
Resumo: BACKGROUND: The liver is an important organ for its ability to transform xenobiotics, making the liver tissue a prime target for toxic substances. The carotenoid bixin present in annatto is an antioxidant that can protect cells and tissues against the deleterious effects of free radicals. In this study, we evaluated the protective effect of bixin on liver damage induced by carbon tetrachloride (CCl4) in rats. RESULTS: The animals were divided into four groups with six rats in each group. CCl4 (0.125 mL kg-1 body wt.) was injected intraperitoneally, and bixin (5.0 mg kg-1 body wt.) was given by gavage 7 days before the CCl4 injection. Bixin prevented the liver damage caused by CCl4, as noted by the significant decrease in serum aminotransferases release. Bixin protected the liver against the oxidizing effects of CCl4 by preventing a decrease in glutathione reductase activity and the levels of reduced glutathione and NADPH. The peroxidation of membrane lipids and histopathological damage of the liver was significantly prevented by bixin treatment. CONCLUSION: Therefore, we can conclude that the protective effect of bixin against hepatotoxicity induced by CCl4 is related to the antioxidant activity of the compound.
Descritores: Tetracloreto de Carbono/antagonistas & inibidores
Carotenoides/farmacologia
Espécies Reativas de Oxigênio/análise
Estresse Oxidativo/efeitos dos fármacos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle
Antioxidantes/farmacologia
-Extratos Vegetais/química
Peroxidação de Lipídeos/efeitos dos fármacos
Carotenoides/química
Ratos Wistar
Bixaceae/química
Doença Hepática Induzida por Substâncias e Drogas/metabolismo
Doença Hepática Induzida por Substâncias e Drogas/patologia
Glutationa/análise
Glutationa Redutase/efeitos dos fármacos
Transaminases/sangue
Fígado/enzimologia
Malondialdeído/análise
NADP/análise
Limites: Animais
Masculino
Ratos
Responsável: CL1.1 - Biblioteca Central


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Id: biblio-843447
Autor: Lucas, Márcio Luís; Carraro, Cristina Campos; Belló-Klein, Adriane; Kalil, Antonio Nocchi; Aerts, Newton.
Título: Oxidative stress in human aorta of patients with advanced aortoiliac occlusive disease
Fonte: Rev. bras. cir. cardiovasc = Braz. j. cardiovasc. surg. (impr.);31(6):428-433, Nov.-Dec. 2016. tab, graf.
Idioma: en.
Resumo: Abstract Introduction: Oxidative stress seems to be a role in the atherosclerosis process, but research in human beings is scarce. Objective: To evaluate the role of oxidative stress on human aortas of patients submitted to surgical treatment for advanced aortoiliac occlusive disease. Methods: Twenty-six patients were divided into three groups: control group (n=10) formed by cadaveric organ donors; severe aortoiliac stenosis group (patients with severe aortoiliac stenosis; n=9); and total aortoiliac occlusion group (patients with chronic total aortoiliac occlusion; n=7). We evaluated the reactive oxygen species concentration, nicotinamide adenine dinucleotide phosphate-oxidase, superoxide dismutase and catalase activities as well as nitrite levels in samples of aortas harvested during aortofemoral bypass for treatment of advanced aortoiliac occlusive disease. Results: We observed a higher level of reactive oxygen species in total aortoiliac occlusion group (48.3±9.56 pmol/mg protein) when compared to severe aortoiliac stenosis (33.5±7.4 pmol/mg protein) and control (4.91±0.8 pmol/mg protein) groups (P<0.05). Nicotinamide adenine dinucleotide phosphate oxidase activity was also higher in total aortoiliac occlusion group when compared to the control group (3.81±1.7 versus 1.05±0.31 µmol/min.mg protein; P<0.05). Furthermore, superoxide dismutase and catalase activities were significantly higher in the severe aortoiliac stenosis and total aortoiliac occlusion groups when compared to the control cases (P<0.05). Nitrite concentration was smaller in the severe aortoiliac stenosis group in comparing to the other groups. Conclusion: Our results indicated an increase of reactive oxygen species levels and nicotinamide adenine dinucleotide phosphate-oxidase activity in human aortic samples of patients with advanced aortoiliac occlusive disease. The increase of antioxidant enzymes activities may be due to a compensative phenomenon to reactive oxygen species production mediated by nicotinamide adenine dinucleotide phosphate oxidase. This preliminary study offers us a more comprehensive knowledge about the role of oxidative stress in advanced aortoiliac occlusive disease in human beings.
Descritores: Doenças da Aorta/cirurgia
Arteriopatias Oclusivas/cirurgia
Estresse Oxidativo
Artéria Ilíaca/cirurgia
-Doenças da Aorta/enzimologia
Arteriopatias Oclusivas/enzimologia
Superóxido Dismutase/análise
Índice de Gravidade de Doença
Catalase/análise
Estudos de Casos e Controles
NADP/análise
Limites: Humanos
Masculino
Feminino
Adulto
Pessoa de Meia-Idade
Adulto Jovem
Tipo de Publ: Estudo Comparativo
Responsável: BR1.1 - BIREME


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Id: biblio-1052039
Autor: Li, Yanjun; Zhang, Dezhi; Cai, Ningyun; Han, Chao; Mao, Qiang; Wang, Ting; Zhou, Qian; Chen, Ning; Xie, Xixian.
Título: Betaine supplementation improved L-threonine fermentation of Escherichia coli THRD by upregulating zwf (glucose-6-phosphate dehydrogenase) expression
Fonte: Electron. j. biotechnol;39:67-73, may. 2019. graf, tab.
Idioma: en.
Projeto: National Natural Science Foundation of China; . National High Technology Research and Development Program; . China Postdoctoral Science Foundation.
Resumo: BACKGROUND: The supplementation of betaine, an osmoprotective compatible solute, in the cultivation media has been widely used to protect bacterial cells. To explore the effects of betaine addition on industrial fermentation, Escherichia coli THRD, an L-threonine producer, was used to examine the production of L-threonine with betaine supplementation and the underlying mechanism through which betaine functions was investigated. RESULTS: Betaine supplementation in the medium of E. coli THRD significantly improved L-threonine fermentation parameters. The transcription of zwf and corresponding enzyme activity of glucose-6-phosphate dehydrogenase were significantly promoted by betaine addition, which contributed to an enhanced expression of zwf that provided more nicotinamide adenine dinucleotide phosphate (NADPH) for L-threonine synthesis. In addition, as a result of the betaine addition, the betaine-stimulated expression of enhanced green fluorescent protein (eGFP) under the zwf promoter within a plasmid-based cassette proved to be a transcription-level response of zwf. Finally, the promoter of the phosphoenolpyruvate carboxylase gene ppc in THRD was replaced with that of zwf, while L-threonine fermentation of the new strain was promoted by betaine addition. Conclusions: We reveal a novel mode of betaine that facilitates the microbial production of useful compounds. Betaine supplementation upregulates the expression of zwf and increases the NADPH synthesis, which may be beneficial for the cell growth and thereby promote the production of L-threonine. This finding might be useful for the production of NADPH-dependent amino acids and derivatives in E. coli THRD or other E. coli strains.
Descritores: Treonina/metabolismo
Betaína/metabolismo
Escherichia coli/metabolismo
-Osmose
Via de Pentose Fosfato
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Escherichia coli/enzimologia
Fermentação
Glucosefosfato Desidrogenase/metabolismo
NADP
Responsável: CL1.1 - Biblioteca Central


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Id: biblio-951609
Autor: Zhu, X; Pan, L; Xiao, T; Ren, X; Liu, Z.
Título: Exogenous niacin treatment increases NADPH oxidase in kiwifruit / O tratamento com niacina exógena NADPH oxidase em kiwis
Fonte: Braz. j. biol;78(4):686-690, Nov. 2018. graf.
Idioma: en.
Resumo: Abstract Kiwifruit are a popular fruit worldwide; however, plant growth is threatened by abiotic stresses such as drought and high temperatures. Niacin treatment in plants has been shown to increase NADPH levels, thus enhancing abiotic stresses tolerance. Here, we evaluate the effect of niacin solution spray treatment on NADPH levels in the kiwifruit cultivars Hayward and Xuxiang. We found that spray treatment with niacin solution promoted NADPH and NADP+ levels and decreased both O2·- production and H2O2 contents in leaves during a short period. In fruit, NADPH contents increased during early development, but decreased later. However, no effect on NADP+ levels has been observed throughout fruit development. In summary, this report suggests that niacin may be used to increase NADPH oxidases, thus increasing stress-tolerance in kiwifruit during encounter of short-term stressful conditions.

Resumo Kiwis são uma fruta popular em todo o mundo; No entanto, o crescimento das plantas é ameaçado por estresses abióticos como a seca e as altas temperaturas. O tratamento com niacina em plantas mostrou aumentar os níveis de NADPH, aumentando assim a tolerância a stress abiótico. Aqui, avaliamos o efeito do tratamento com spray de solução de niacina sobre os níveis de NADPH nos cultivares de kiwis Hayward e Xuxiang. Descobrimos que o tratamento por spray com solução de niacina promoveu níveis de NADPH e NADP + e diminuiu a produção de O2·- e os teores de H2O2 nas folhas durante um curto período. Nos frutos, os teores de NADPH aumentaram durante o desenvolvimento precoce, mas diminuíram mais tarde. No entanto, não se observou qualquer efeito nos níveis de NADP + ao longo do desenvolvimento do fruto. Em resumo, este relatório sugere que a niacina pode ser utilizada para aumentar NADPH oxidases, aumentando assim a tolerância ao estresse em kiwis durante o encontro de condições estressantes de curto prazo.
Descritores: NADPH Oxidases/efeitos dos fármacos
Actinidia/efeitos dos fármacos
Frutas/efeitos dos fármacos
Niacina/farmacologia
-Oxirredução
Folhas de Planta/efeitos dos fármacos
Folhas de Planta/metabolismo
Radicais Livres/metabolismo
Frutas/crescimento & desenvolvimento
NADP/metabolismo
Responsável: BR1.1 - BIREME


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Id: biblio-1054682
Autor: Li, Yanze; Wang, Lei; Chen, Zhiyuan; Liu, Xiuheng.
Título: Picroside II attenuates ischemia/reperfusion testicular injury by alleviating oxidative stress and apoptosis through reducing nitric oxide synthesis
Fonte: Acta cir. bras;34(11):e201901102, Nov. 2019. tab, graf.
Idioma: en.
Projeto: Application and Basic Research Project of Wuhan City; . Wuhan Morning Light Plan of Youth Science and Technology; . Natural Science Foundation of Hubei Province; . Research Project of Wuhan University.
Resumo: Abstract Purpose: To investigate the effect of Picroside II on testicular ischemia and reperfusion (l/R) injury and the underlying mechanism. Methods: Sprague-Dawley rats were randomly divided into 4 groups: sham operated group (Sham), Sham with Picroside II treatment group (Sham+ Pic II), l/R group (l/R) and l/R with Picroside II treatment group (I/R+ Pic II). l/R model was established by rotating the left testis 720° in a clock-wise direction for 4 hours. The histopathologic and spermatogenetic evaluation was performed. The apoptosis changes and the levels of HO-1 (heme oxygenase-1), MPO (myeloperoxidase), NOX (NADPH oxidase), SOD (superoxide dismutase), XO (xanthine oxidase) and NOS (nitric oxide synthase) were measured. Results: The seminiferous tubules were damaged in l/R rats, but Picroside II alleviated the changes induced by l/R. The increased level of apoptosis was decreased by Picroside II (P=0.01, 9.05±0.35 vs. 4.85±0.25). The activities of HO-1, MPO, NOX, XO and MDA content were increased and the SOD activity was decreased in l/R (P<0.05) and could be reversed by Picroside II (P=0.03, 405.5±7.5 vs. 304±17U/mgprot; P=0.02, 0.99±0.05 vs. 0.52±0.04 mgprot; P=0.01, 260+7 vs. 189±2 mgprot; P=0.04, 10.95+0.55 vs. 8.75+0.35 U/mgprot; P=0.045, 6.8+0.7 vs. 3.75+0.35 mgprot; P=0.04, 44.5+3.5 vs. 57.5+3.5 mgprot). Western blot showed that the expression of iNOS, nNOS and eNOS were increased in l/R (P<0.05); however, they were decreased after Picroside II treatment (P<0.05). Conclusion: Picroside II attenuated testicular I/R injury in rats mainly through suppressing apoptosis and oxidative stress through reduction of nitric oxide synthesis.
Descritores: Testículo/irrigação sanguínea
Traumatismo por Reperfusão/prevenção & controle
Cinamatos/farmacologia
Apoptose/efeitos dos fármacos
Estresse Oxidativo/efeitos dos fármacos
Glucosídeos Iridoides/farmacologia
Óxido Nítrico/biossíntese
-Traumatismo por Reperfusão/metabolismo
Traumatismo por Reperfusão/patologia
Distribuição Aleatória
Western Blotting
Ratos Sprague-Dawley
Peroxidase/análise
Marcação In Situ das Extremidades Cortadas
Heme Oxigenase-1/análise
Malondialdeído/análise
NADP/análise
Limites: Animais
Masculino
Tipo de Publ: Estudo de Avaliação
Responsável: BR1.1 - BIREME


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Id: biblio-951808
Autor: Zhang, Sen; Song, Ping; Li, Shuang.
Título: Application of n-dodecane as an oxygen vector to enhance the activity of fumarase in recombinant Escherichia coli: role of intracellular microenvironment
Fonte: Braz. j. microbiol;49(3):662-667, July-Sept. 2018. tab, graf.
Idioma: en.
Projeto: Natural Science Foundation of Jiangsu Province; . National science fund for colleges and universities in Jiangsu Province.
Resumo: Abstract The effect of the intracellular microenvironment in the presence of an oxygen vector during expression of a fusion protein in Escherichia coli was studied. Three organic solutions at different concentration were chosen as oxygen vectors for fumarase expression. The addition of n-dodecane did not induce a significant change in the expression of fumarase, while the activity of fumarase increased significantly to 124% at 2.5% n-dodecane added after 9 h induction. The concentration of ATP increased sharply during the first 6 h of induction, to a value 7600% higher than that in the absence of an oxygen-vector. NAD/NADH and NADP/NADPH ratios were positively correlated with fumarase activity. n-Dodecane can be used to increase the concentration of ATP and change the energy metabolic pathway, providing sufficient energy for fumarase folding.
Descritores: Oxigênio/metabolismo
Expressão Gênica
Alcanos/metabolismo
Escherichia coli/genética
Fumarato Hidratase/metabolismo
-Oxigênio/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Proteínas Recombinantes/química
Dobramento de Proteína
Alcanos/química
Escherichia coli/metabolismo
Fumarato Hidratase/genética
Fumarato Hidratase/química
NADP/metabolismo
NADP/química
Responsável: BR1.1 - BIREME


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Id: lil-792407
Autor: Lucas, Márcio Luís; Carraro, Cristina Campos; Belló-Klein, Adriane; Kalil, Antônio Nocchi; Aerts, Newton.
Título: Oxidative stress in carotid arteries of patients submitted to carotid endarterectomy. The role of aging process
Fonte: Acta cir. bras;31(8):564-568, Aug. 2016. tab, graf.
Idioma: en.
Resumo: ABSTRACT PURPOSE: To evaluated the role of oxidative stress on aging process in patients submitted to carotid endarterectomy. METHODS: Twenty patients were divided into two groups: older group (≥ 70 years old); and the younger group (< 70 years old). We evaluated the reactive oxygen species (ROS) concentration, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, superoxide dismutase (SOD) and catalase (CAT) activities as so as nitrite levels in fragments of carotid arteries harvested during carotid endarterectomy for treatment of high grade carotid stenosis. RESULTS: We observed a higher levels of ROS and NADPH oxidase activity in the older group (p<0.05). Furthermore, the nitrite concentration was lower in the older group (14.55 ± 5.61 x 10-3 versus 26.42 ± 8.14 x 10-3 µM; p=0.0123). However, the activities of antioxidant enzymes (CAT and SOD) were similar in both the groups. CONCLUSIONS : Arterial aging is associated with increased concentrations of oxygen species and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity as so as nitrite reduction in human carotid artery specimens. Maybe therapies that block NADPH oxidase activity and enhance nitrite stores would be a good strategy to reduce the effect of oxidative stress in arterial aging.
Descritores: Envelhecimento/fisiologia
Artérias Carótidas/fisiologia
Endarterectomia das Carótidas
Estresse Oxidativo/fisiologia
-Superóxido Dismutase/metabolismo
Doença da Artéria Coronariana/cirurgia
Artérias Carótidas/enzimologia
Catalase/metabolismo
Espécies Reativas de Oxigênio/análise
NADP/análise
Limites: Humanos
Masculino
Feminino
Pessoa de Meia-Idade
Idoso
Idoso de 80 Anos ou mais
Responsável: BR1.1 - BIREME


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Id: biblio-881315
Autor: Letelier, María E; Iturra-Montecinos, Pablo A; Gallardo-Garrido, Carlos A.
Título: Herbal extracts differentially inhibit oxidative effects caused by the biotransformation of nifurtimox, nitrofurantoin and acetaminophen on rat liver microsomes / Extractos herbales inhiben diferencialmente los efectos oxidativos causados por la biotransformación de nifurtimox, nitrofurantoína y acetaminofeno en microsomas hepáticos de rata]
Fonte: Bol. latinoam. Caribe plantas med. aromát;16(2):88-98, mar. 2017. tab, graf.
Idioma: en.
Resumo: Inflammation is a cellular defensive mechanism associated to oxidative stress. The administration of nitrofurantoin, nifurtimox and acetaminophen generates oxidative stress by their biotransformation through CYP450 system. The main adverse effect described for the first two drugs is gastrointestinal inflammation and that of the last, hepatitis. Therefore, standardised dry extracts from Rosmarinus officinalis, Buddleja globosa Hope, Cynara scolymus L., Echinacea purpurea and Hedera helix were tested to evaluate their capacity to decrease drug-induced oxidative stress. For that, rat liver microsomes were incubated with drugs in the presence of NADPH (specific CYP450 system cofactor) to test oxidative damage on microsomal lipids, thiols, and GST activity. All drugs tested induced oxidation of microsomal lipids and thiols, and inhibition of GST activity. Herbal extracts prevented these phenomena in different extension. These results show that antioxidant phytodrugs previously evaluated could alleviate drugs adverse effects associated to oxidative stress.

Inflamación es un mecanismo de defensa el cual está asociado a estrés oxidativo. La administración de nitrofurantoína, nifurtimox y paracetamol genera estrés oxidativo al metabolizarse a través del sistema CYP450. El principal efecto adverso de los dos primeros fármacos es inflamación gastrointestinal y del tercero, hepatitis. Por lo tanto, utilizamos diversos extractos herbales para disminuir el estrés oxidativo inducido por estos fármacos. Para esto se incubaron microsomas hepáticos de rata con dichos fármacos en presencia de NADPH (cofactor específico del sistema CYP450) y se evaluó el daño oxidativo generado sobre los lípidos, los tioles y la actividad GST microsómica. Todos los fármacos indujeron oxidación de los lípidos y los tioles microsómicos e inhibieron la actividad GST. Los extractos herbales previnieron estos fenómenos oxidativos en diferente extensión. Estos resultados indican que fitofármacos antioxidantes previamente evaluados, podrían aliviar los efectos adversos asociados a estrés oxidativo de los fármacos.
Descritores: Antioxidantes/farmacologia
Microssomos Hepáticos/efeitos dos fármacos
Estresse Oxidativo/efeitos dos fármacos
Extratos Vegetais/farmacologia
-Acetaminofen/efeitos adversos
Glutationa Transferase/metabolismo
Peroxidação de Lipídeos
Microssomos Hepáticos/enzimologia
NADP/análise
Nifurtimox/efeitos adversos
Nitrofurantoína/efeitos adversos
Extratos Vegetais/química
Polifenóis/análise
Ratos Sprague-Dawley
Compostos de Sulfidrila
Limites: Animais
Masculino
Responsável: CL1.1 - Biblioteca Central


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Id: lil-794145
Autor: Vélez Tobón, Gabriel Jaime; Rocha Arrieta, Yermis Carolina; Arias Sierra, Andrés Augusto; López Quintero, Juan Álvaro.
Título: Función del sistema NADPH oxidasa en la formación de trampas extracelulares de los neutrófilos (NETs) / Role of nadph oxidase system in the neutrophil extracelular Traps (NETs) formation
Fonte: Rev. cuba. hematol. inmunol. hemoter;32(1):43-56, ene.-mar. 2016. ilus, tab.
Idioma: es.
Resumo: Las trampas extracelulares de los neutrófilos son estructuras fundamentalmente compuestas de cromatina y proteínas granulares, que una vez liberadas constituyen un mecanismo de defensa que tiene la capacidad de atrapar y destruir microorganismos patógenos. El proceso que libera estas estructuras es conocido como NETosis y en el caso que provoque muerte celular, esta es diferente a la apoptosis y a la necrosis. Si bien no se conocen todos los eventos moleculares involucrados en la formación de las NETs, se sabe que dependiendo del estímulo, las especies reactivas del oxígeno son esenciales para que ocurra la descondensación de la cromatina y se lleve a cabo el proceso de NETosis(AU)

Neutrophil extracellular traps (NETs) are structures mainly composed of chromatin and granule proteins that once released constitute a defense mechanism due to their ability to trap and destroy pathogen microorganisms. The process by which these structures are released is known as NETosis and in case this may lead to cell death is different to apoptosis and necrosis. Although all the molecular events involved in the formation of NETs are poorly understood, it is known that depending on the stimulus, reactive oxygen species (ROS) are essential to the chromatin decondensation and subsequent NETs formation(AU)
Descritores: Armadilhas Extracelulares
NADP/fisiologia
Neutrófilos/imunologia
-Doença Granulomatosa Crônica/tratamento farmacológico
Doença Granulomatosa Crônica/genética
Limites: Humanos
Tipo de Publ: Revisão
Responsável: CU1.1 - Biblioteca Médica Nacional


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Id: lil-756636
Autor: Silva, João Alfredo de Moraes Gomes.
Título: Modulação redox da homeostase de células musculares lisas através de estimuladores do sistema NADPH oxidase / Redox modulation of smooth muscle cells homeostasis via inductors of NADPHoxidase system.
Fonte: Rio de Janeiro; s.n; 2011. 108 f p.
Idioma: pt.
Tese: Apresentada a Universidade do Estado do Rio de Janeiro - Instituto de Biologia Roberto Alcântara Gomes para obtenção do grau de Doutor.
Resumo: As doenças cardiovasculares representam a principal causa de morte nos países ocidentais. Dentre essas doenças, a aterosclerose é que mais se destaca, sendo caracterizada pelo acúmulo de células musculares lisas vasculares (CMLV). O efeito patológico das CMLV em resposta a diferentes estímulos pode acarretar em disfunções nestas células. É notável que a aterosclerose ocorra principalmente em vasos sinuosos onde ocorre um forte turbilhonamento do fluxo sanguíneo, que pode acarretar em hemólise e, consequentemente, acúmulo de heme livre. Além disso, no processo de aterogênese as moléculas de adesão, principalmente integrinas, são de crucial importância durante a resposta de CMLV. Nesse trabalho nosso objetivo inicial foi avaliar o efeito do heme livre nas funções de CMLV, bem como os mecanismos moleculares por trás desses efeitos. Em uma segunda parte, investigamos o envolvimento da integrina α1ß1 no efeito da Angiotensina II (Ang II) em CMLV. Nós observamos que o heme livre é capaz de induzir a proliferação e migração de CMLV via espécies reativas de oxigênio (ERO) provenientes da NADPHoxidase (NADPHox). Adicionalmente vimos que o heme ativa vias de sinalização redox-sensíveis relacionadas à proliferação celular, como MAPKinases e o fator de transcrição NFκB. Também observamos que há uma ligação entre a NADPHox e o sistema heme oxigenase (HO), uma vez que o heme induz a expressão de HO-1 e o pré-tratamento das CMLV com inibidores de HO levam ao aumento tanto o efeito proliferação quanto a indução de ERO promovidas pelo heme. Além disso, vimos que o efeito contra-regulatório promovido pela HO ocorre devido as metabolites do heme: biliverdina, bilirrubina e monóxido de carbono. Por último, quando bloqueamos tanto a NADPHox quanto o sistema HO o heme não teve efeito algum na proliferação de CMLV...

Cardiovascular diseases represent the major mortality reason in western countries. Among these diseases, atherosclerosis is the most prominent one, which is characterized by vascular smooth muscle cell (VSMC) accumulation. The pathological effect of VSMC in response to different stimuli is able to induce VSMC dysfunctions. Notably, this cardiovascular disease occurs mainly in sinuous vessels with turbulent blood flow, which may lead to hemolysis and consequent free heme accumulation. Furthermore, in atherogenesis the adhesion molecule, mainly integrins, were of crucial importance during the VSMC response. In this work our aim was to elucidate the effect of free heme in VSMC, as well the molecular mechanisms underlying this process. In a second part, we investigated the role of α1ß1 integrin in Angiotensin II (Ang II) effect on VSMC. We observed that free heme is able to induce VSMC proliferation in a Reactive Oxygen Species (ROS) derived from NADPHoxidase (NADPHox) dependent manner. Additionally, heme activates proliferation-relationed redox-sensitive signaling routes, such as MAPKinases and the transcription factor NFκB. It was also observed a critical crosstalk between NADPHox and heme oxygenase (HO) system, once heme induces HO-1 expression and VSMC pretreatment with HO inhibitors increased heme proliferative effect and ROS production. Accordingly, we observed that the counter-regulatory effect promoted by HO occurs due heme metabolites: biliverdin, bilirubin and carbon monoxide. Finally, when both NADPHox and HO system were blocked, heme had no effect on VSMC proliferation...
Descritores: Aterosclerose/patologia
Doenças Cardiovasculares/fisiopatologia
Heme
Homeostase
Músculo Liso Vascular/fisiopatologia
NADP
-Modulação Antigênica
Aterosclerose/prevenção & controle
Heme Oxigenase-1
Integrinas/fisiologia
Músculo Liso Vascular/citologia
Limites: Humanos
Responsável: BR1365.1 - Biblioteca Biomédica A - CB/A



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