Caracterização bioquímica e efeitos metabólicos do factor de necrose tumoral

• Autor(a) principal: Martins e Silva, J.
• Data de Publicação: 1991
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10451/20156

The tumor necrosis factor, preliminary identified because of its antitumor properties, refers to two kinds of similar polypeptides (TNF or cachectin, and TNF-fl or lymphotoxin), which share some biolo gical effects. Both substances, as members of the class of cytokines, play a role as mediators of inflam mation and the celiular immune response. Human cachectin is produced as a prohormone and activated by cleavage of a 76 residue peptide. Mature cachectin (with comprises 157 aminoacid residues) share a 28% aminoacid sequence homology with lymphotoxin. Both cytokines are encoded by different genes of chromosome 6 and may compete for a common receptor. Cachectin is produced by a wide variety of cells (phagocytic and non-phagocytic), mainly by activated macrophages and monocytes. Different inva sive stimuli (mainly lipopolysaccharide, a constituent of the Gram-negative bacteria’s outer wall) acti vate cachectin biosynthesis, which is controlled chiefly at a post-transcriptional levei. The newiy synthetised cachectin remains associated as a transmembrane form, affecting their targets by direct celi-to-cell contact, or is actively secreted in the circuiation to distant sites in the body, where it binds to high affinity cachectin receptor, on a variety of ccli types. Cachectin exerts pleiotropic effects on nor mal, transformed, or tumoral celis. The biological effects mediate by cachectin may be beneficial or deleterious to the body, depending on the quantity produced, duration of ccli exposure and further biochemical mediators in the enviromment of the target edis. Cachexin (frequently associated with severe infection and cancer) seems to be the result of a persistent exposure to raised leveis of cachectin. This cytokine reguiates the activities of different enzymes, thus increasing adipocyte lypolysis and skele tal myocyte glucose catabolism. and increasing hepatocyte gluconeogenesis and acute-phase protein biosynthesis. A very suggestive effect of cachectin is the anti-tumor activity. This cytotoxic-cytolytic effect include hemorrhage and necrosis of some tumor species through mechanisms still open to discus sion. Eventually, two steps may be suggested, one that renders the tumor vessels susceptible to damage with subsequent hemorrhage, the second directly affecting the tumor cells. causing the cdl death. inhibi ting cdl growth, or with no effect. However the therapeutical application of cachectin in cancer is still at preliminary stages and requires further studies that eluciate better the mechanism of action of that cytokinc and eliminate most of its secondary toxicity..