Navegando por Palavras-chave "Anexina"

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    Análises gênica e proteica da anexina 1 na biologia do desenvolvimento e na fisiopatologia da inflamação
    (Universidade Federal de São Paulo (UNIFESP), 2006-01-01) Damazo, Amilcar Sabino [UNIFESP]; Oliani, Sonia Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The annexin 1 (ANXA1) is a 37 kDa protein that has been implicated in the regulation of phagocytosis, cell signaling, apoptosis and leukocyte transmigration. Originally described as a phospholipase A2-inhibitory protein, ANXA1 can regulate several components of the inflammatory reaction, such as cytokines. Recently, a line of animals lacking the AnxA1 gene was generated with dual purpose targeting construct, designed simultaneously to inactivate the AnxA1 gene and to report upon its activity using LacZ reporter gene. In the developmental biology, the epithelial and leukocytes, studied in different organs, display AnxA1 gene expression. In the liver, the hepatocytes synthesize this protein during the embriogenesis, disappearing in adults. In those animals, the ANXA1 is re-synthesized during cancer, regeneration or inflammatory process. In the intramembranous ossification, the densitometric and histological analysis of newborn ANXA1 null skull bones showed that the absence of the ANXA1 induced a delay in this process. In models of experimental acute inflammation, ANXA1 null mice exhibited an exaggerated response and a partial or complete resistance to the anti-inflammatory effects of glucocorticoids. Several other anomalies were noted, including increased spontaneous migratory behavior of leukocytes and mast cell degranulation. Also, the absence of ANXA1 during the acute inflammation induce a disregulation in the leukocyte expression of adhesion molecules, such as selectin CD26L and integrin CD11b, leading to a higher cell adhesion in the ANXA1 null mice. During the endotoxemic response, the ANXA1 null mice exhibited a toxic response characterized by a marked degree of leukocyte adhesion and an aberrant expression of Toll-like receptor 4 in macrophages. These alterations have resulted in organ injury and lethality within 48 hours, a phenotype rescued by exogenous administration of ANXA1. Finally, the pleiotropic and pluripotent role of ANXA1 may be explained by the phosphorylation of its N-terminal domain, which induces specific actions, for example the regulation of cell growth, the vesicles aggregation, and the translocation of ANXA1 to cell membrane. In conclusion, the study of ANXA1 genic and proteic activities in the developmental biology or in the homeostasis of the inflammatory response might design the development of novel anti-inflammatory therapeutics based on this endogenous mediator.