Navegando por Palavras-chave "lysosomes"
Agora exibindo 1 - 3 de 3
Resultados por página
Opções de Ordenação
- ItemAcesso aberto (Open Access)Emerging concepts about NAIP/NLIRC4 inflammasomes(Frontiers Research Foundation, 2014-07-02) Lage, Silvia Lucena [UNIFESP]; Longo, Carla [UNIFESP]; Branco, Laura Migliari [UNIFESP]; Costa, Thais Boccia da [UNIFESP]; Buzzo, Carina de Lima [UNIFESP]; Bortoluci, Karina Ramalho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Neuronal apoptosis inhibitory protein (NAIP)/NOD-like receptor (NLR) containing a caspase activating and recruitment domain (CARD) 4 (NLRC4) inflammasome complexes are activated in response to proteins from virulent bacteria that reach the cell cytosol. Specific NAIP proteins bind to the agonists and then physically associate with NLRC4 to form an inflammasome complex able to recruit and activate pro-caspase-1. NAIP5 and NAIP6 sense flagellin, component of flagella from motile bacteria, whereas NAIP1 and NAIP2 detect needle and rod components from bacterial type III secretion systems, respectively. Active caspase-1 mediates the maturation and secretion of the pro-inflammatory cytokines, 11,113 and 11,18, and is responsible for the induction of pyroptosis, a pro-inflammatory form of cell death. in addition to these well-known effector mechanisms, novel roles have been described for NAIP/NLRC4 inflammasomes, such as phagosomal maturation, activation of inducible nitric oxide synthase, regulation of autophagy, secretion of inflammatory mediators, antibody production, activation of T cells, among others. These effector mechanisms mediated by NAIP/NLRC4 inflammasomes have been extensively studied in the context of resistance of infections and the potential of their agonists has been exploited in therapeutic strategies to non-infectious pathologies, such as tumor protection. Thus, this review will discuss current knowledge about the activation of NAIP/NLRC4 inflammasomes and their effector mechanisms.
- ItemSomente MetadadadosEstrogenic activity of tamoxifen on normal mammary parenchyma in the luteal phase of the menstrual cycle(Elsevier B.V., 1997-01-01) Facina, G.; deLima, G. R.; Simoes, M. J.; Novo, N. F.; Gebrim, L. H.; Universidade Federal de São Paulo (UNIFESP)Objectives: Tamoxifen, an anti-estrogenic drug used in the adjuvant treatment of breast cancer, deserves more investigation for the determination of its efficacy as a prophylactic agent against breast cancer in high risk women. Thus, the action of tamoxifen on the human mammary gland was studied by measuring the number of lysosomes in normal mammary epithelium during the administration of tamoxifen. Methods: Tamoxifen was administered only during the luteal phase of the menstrual cycle to avoid interference with corpus luteum formation. A fragment of breast tissue adjacent to a fibroadenoma was obtained during surgery from 35 premenopausal women aged 15 to 37 years who had been eumenorrheic for at least 6 months; 18 of these patients were treated with tamoxifen and 17 were used as controls. Lysosome counts were performed under the light microscope on slides submitted to the acid phosphatase cytochemical technique and the data were analyzed statistically by the Mann-Whitney test. Results: the fragments from the group treated with tamoxifen showed a significant decrease in lysosome numbers. Conclusions. Tamoxifen administered after ovulation significantly decreases the number of lysosomes in the cells of normal mammary epithelium, demonstrating the antiestrogenic effect of the drug on this target tissue. (C) 1997 International Federation of Gynecology and Obstetrics.
- ItemSomente MetadadadosMecanismo de ação do composto paladaciclo ferroceno 1:2 em modelos celulares de resistência e metástase tumoral(Universidade Federal de São Paulo (UNIFESP), 2016-06-30) Bechara, Alexandre [UNIFESP]; Trindade, Claudia Bincoletto Trindade [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Cancer therapy is one of the major challenges for medicine since 20th century, when the mechanisms of tumor cell biology in cancer development began to be better understood. Although some pharmacological therapeutic strategies can lead to complete remission, the vast majority of cases eventually relapses and develops into distant metastases, making the pharmacological therapeutic of cancer a complexity theme. The comprehensive understanding of the cellular cues and molecular pathways involved in cell death during new drugs development and more effective therapy approaches are needed. Given the above, this study aimed to elucidate the cellular and molecular mechanisms of the palladacycle Ferrocene 1: 2 (PF12) compound, an emerging antitumor drug prototype, on human osteosarcoma (SaOS-2) and murine melanoma (B16F10 Nex2) cells. These cells lines (SaOS-2 and B16F10Nex2) were used as a model for tumor resistance to conventional anticancer therapy and metastasis, respectively. Through in vitro assays, we found that PF12 has a complex cellular mechanism due mainly, its lysosomotropic features. This cellular effect was associated with the presence of the ferrocene group in its molecule. As a result of the PF12 effects on lysosomes, vesicular acids compartments reduction was observed with the release of calcium from lysosomal stores with extravasation of cathepsin B too. Both (calcium and cathepsin B) have emerged as crucial factors in the cytotoxicity of the compound in Saos-2 cells as their inhibition before PF12 exposure decreased PF12-induced Saos-2 cell death. Furthermore, PF12 induced autophagy in these cells, which appears to occur as a response to the induced damage. Nevertheless, we found that PF12 also showed significant antitumor activity in vivo, reducing the number of lung nodules of melanoma cells in mice. In vitro studies with melanoma cells have demonstrated a cytotoxic action in 24 hours incubation and an inhibitory activity on the tumor cells migration and invasion after 1 hour of exposure. It was also observed that both inhibition and induction of autophagy in this cells (B16F10-Nex2 ) enhanced PF12 cytotoxicity. In cell migration process, when autophagy induction was followed by PF12 exposure, B16F10-Nex2 cells migration ability was significantly reduced. In relation to cellular invasion process, autophagy induction increased cell invasiveness, and the associations between autophagy inhibitor with PF12 and autophagy induction followed by PF12 exposure significantly reduced compound's anti-invasiveness activity. Considering all obtained data, we conclude that PF12 shows significant effectiveness as a cytotoxic compound with the capacity to interact with multiple targets, as well as to consider as a possible ant metastatic agent.