RESUMO
Database URL: http://yaam.ifc.unam.mx/.
Assuntos
Aminoácidos/genética , Bases de Dados de Proteínas , Processamento de Proteína Pós-Traducional/fisiologia , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Ferramenta de Busca , Aminoácidos/metabolismo , Biossíntese de Proteínas/fisiologia , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/biossínteseRESUMO
Photothermal therapy has shown to be a promising technique for local treatment of tumors. However, the main challenge for this technique is the availability of localized heat sources to minimize thermal damage in the surrounding healthy tissue. In this work, we demonstrate the use of optical fiber microheaters for inducing thermal lesions in soft tissue. The proposed devices incorporate carbon nanotubes or gold nanolayers on the tips of optical fibers for enhanced photothermal effects and heating of ex vivo biological tissues. We report preliminary results of small size photothermal lesions induced on mice liver tissues. The morphology of the resulting lesions shows that optical fiber microheaters may render useful for delivering highly localized heat for photothermal therapy.
RESUMO
The mammalian target of rapamycin, best known as mTOR, is a phylogenetically conserved serine/threonine kinase that controls life-defining cellular processes such as growth, metabolism, survival, and migration under the influence of multiple interacting proteins. Historically, the cellular activities blocked by rapamycin in mammalian cells were considered the only events controlled by mTOR. However, this paradigm changed with the discovery of two signaling complexes differentially sensitive to rapamycin, whose catalytic component is mTOR. The one sensitive to rapamycin, known as mTORC1, promotes protein synthesis in response to growth factors and nutrients via the phosphorylation of p70S6K and 4EBP1; while the other, known as mTORC2, promotes cell migration and survival via the activation of Rho GTPases and the phosphorylation of AKT, respectively. Although mTORC2 kinase activity is not inhibited by rapamycin, hours of incubation with this antibiotic can impede the assembly of this signaling complex. The direct mechanism by which mTORC2 leads to cell migration depends on its interaction with P-Rex1, a Rac-specific guanine nucleotide exchange factor, while additional indirect pathways involve the intervention of PKC or AKT, multifunctional ubiquitous serine/threonine kinases that activate effectors of cell migration upon being phosphorylated by mTORC2 in response to chemotactic signals. These mTORC2 effectors are altered in metastatic cancer. Numerous clinical trials are testing mTOR inhibitors as potential antineoplasic drugs. Here, we briefly review the actions of mTOR with emphasis on the controlling role of mTORC1 and mTORC2-interacting proteins and highlight the mechanisms linked to cell migration.
Assuntos
Metabolismo Energético/fisiologia , Modelos Biológicos , Transdução de Sinais/fisiologia , Sirolimo/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Movimento Celular/fisiologia , Proliferação de Células , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina , Complexos MultiproteicosRESUMO
AII (angiotensin II) is a vasoactive peptide that plays an important role in the development of liver fibrosis mainly by regulating profibrotic cytokine expression such as TGF-beta (transforming growth factor-beta). Activated HSCs (hepatic stellate cells) are the major cell type responsible for ECM (extracellular matrix) deposition during liver fibrosis and are also a target for AII and TGF-beta actions. Here, we studied the effect of AII on the mRNA levels of TGF-beta isoforms in primary cultures of rat HSCs. Both quiescent and activated HSCs were stimulated with AII for different time periods, and mRNA levels of TGF-beta1, TGF-beta2 and TGF-beta3 isoforms were evaluated using RNaseI protection assay. The mRNA levels of all TGF-beta isoforms, particularly TGF-beta2and TGF-beta3, were increased after AII treatment in activated HSCs. In addition, activated HSCs were able to produce active TGF-beta protein after AII treatment. The mRNA expression of TGF-beta isoforms induced by AII required both ERK1/2 and Nox (NADPH oxidase) activation but not PKC (protein kinase C) participation. ERK1/2 activation induced by AII occurs via AT1 receptors, but independently of either PKC and Nox activation or EGFR (epidermal growth factor receptor) transactivation. Interestingly, AII has a similar effect on TGF-beta expression in quiescent HSCs, although it has a smaller but significant effect on ERK1/2 activation in these cells.
Assuntos
Angiotensina II/metabolismo , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/metabolismo , RNA Mensageiro/análise , Receptor Tipo 1 de Angiotensina/genética , Fator de Crescimento Transformador beta/genética , Animais , Western Blotting , Células Cultivadas , Matriz Extracelular/metabolismo , Luciferases , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Regulação para CimaRESUMO
Collagen-polyvinylpyrrolidone (Collagen-PVP) has been demonstrated to elicit immunomodulatory properties in different chronic inflammatory diseases. Nevertheless, its effects on asthma are still unknown. We have evaluated whether collagen-PVP could modulate airway inflammation and remodelling in a guinea pig model of allergic asthma. Sensitized guinea pigs were challenged with the allergen (ovalbumin) six times (at 10-day intervals). From the third challenge on, animals were treated every 5 days with saline aerosols containing 0.16, 0.33, or 0.66 mg/ml of collagen-PVP (n = 5, respectively). Some guinea pigs, sensitized and challenged with saline as well as treated with 0 or 0.66 mg/ml collagen-PVP, were included in the study as control (n = 7) and sham groups (n = 5), respectively. From the first challenge on, ovalbumin induced a transient airway obstruction, measured by barometric plethysmography, which was not modified by collagen-PVP treatments. After the last allergen challenge, guinea pigs were anesthetized to obtain bronchoalveolar lavage (BAL) and the left lung caudal lobe. As expected, BAL cell count from allergen-challenged guinea pigs showed abundant neutrophils and eosinophils, as well as numerous tumor necrosis factor (TNF)-alpha-expressing granulocytes and macrophages in airway wall (determined by immunohistochemical assay). Neutrophilia and TNF-alpha-expressing leukocytes, from collagen-PVP treated animals, diminished from 0.16 mg/ml, and eosinophilia from 0.66 mg/ml of collagen-PVP doses. Histological changes induced by allergen challenges include thickening of connective tissue below airway epithelium and vascular wall widening of airway adjacent vessels; these changes were reduced by collagen-PVP treatment. Collagen-PVP seems to have anti-inflammatory and antifibrotic properties in this guinea pig asthma model.
Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Asma/tratamento farmacológico , Colágeno/administração & dosagem , Pneumonia/terapia , Povidona/administração & dosagem , Administração por Inalação , Aerossóis , Alérgenos , Animais , Asma/imunologia , Asma/fisiopatologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Granulócitos/efeitos dos fármacos , Granulócitos/imunologia , Cobaias , Imuno-Histoquímica , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/imunologia , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Ovalbumina , Pletismografia , Pneumonia/imunologia , Pneumonia/fisiopatologia , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/fisiopatologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
SnoN and Ski oncoproteins are co-repressors for Smad proteins and repress TGF-beta-responsive gene expression. The smad7 gene is a TGF-beta target induced by Smad signaling, and its promoter contains the Smad-binding element (SBE) required for a positive regulation by the TGF-beta/Smad pathway. SnoN and Ski co-repressors also bind SBE but regulate negatively smad7 gene. Ski along with Smad4 binds and represses the smad7 promoter, whereas the repression mechanism by SnoN is not clear. Ski and SnoN overexpression inhibits smad7 reporter expression induced through TGF-beta signaling. Using chromatin immunoprecipitation assays, we found that SnoN binds smad7 promoter at the basal condition, whereas after a short TGF-beta treatment for 15-30 min SnoN is downregulated and no longer bound smad7 promoter. Interestingly, after a prolonged TGF-beta treatment SnoN is upregulated and returns to its position on the smad7 promoter, functioning probably as a negative feedback control. Thus, SnoN also seems to regulate negatively the TGF-beta-responsive smad7 gene by binding and repressing its promoter in a similar way to Ski.