RESUMEN
The protein CD36 is a membrane receptor for thrombospondin (TSP), malaria-infected erythrocytes, and collagen. Three functional sequences were identified within a single disulfide loop of CD36: one that mediates TSP binding (amino acids 87 to 99) and two that support malarial cytoadhesion (amino acids 8 to 21 and 97 to 110). One of these peptides (p87-99) is a consensus protein kinase C (PKC) phosphorylation site. Dephosphorylation of constitutively phosphorylated CD36 in resting platelets and a megakaryocytic cell line led to the loss of collagen adhesion and platelet reactivity to collagen, with a reciprocal increase in TSP binding. PKC-mediated phosphorylation of this ectodomain resulted in a loss of TSP binding and the reciprocal acquisition of collagen binding. In site-directed mutagenesis studies, when the threonine phosphorylation site was changed to alanine, CD36 was expressed in a dephosphorylated state and bound to TSP constitutively.
Asunto(s)
Antígenos CD/metabolismo , Plaquetas/metabolismo , Colágeno/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana Plaquetaria/metabolismo , Secuencia de Aminoácidos , Animales , Antígenos CD/química , Antígenos CD/genética , Secuencia de Bases , Antígenos CD36 , Adhesión Celular , Línea Celular , Eritrocitos/citología , Eritrocitos/parasitología , Humanos , Megacariocitos/metabolismo , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Fosforilación , Plasmodium falciparum/fisiología , Adhesividad Plaquetaria , Agregación Plaquetaria , Glicoproteínas de Membrana Plaquetaria/química , Glicoproteínas de Membrana Plaquetaria/genética , Proteína Quinasa C/metabolismo , Receptores de Citoadhesina/metabolismo , TrombospondinasAsunto(s)
Serodiagnóstico de la Sífilis , Sífilis/epidemiología , Adolescente , Adulto , Brasil , Humanos , Masculino , Factores SocioeconómicosRESUMEN
Addition of a nitrogen-source to glucose-repressed, nitrogen-starved G0 cells of the yeast Saccharomyces cerevisiae in the presence of a fermentable carbon source induces growth and causes within a few minutes a five-fold, protein-synthesis-independent increase in the activity of trehalase. Nitrogen-activated trehalase could be deactivated in vitro by alkaline phosphatase treatment, supporting the idea that the activation is triggered by phosphorylation. Yeast strains containing only one of the three TPK genes (which encode the catalytic subunit of cAMP-dependent protein kinase) showed different degrees of nitrogen-induced trehalase activation. The order of effectiveness was different from that previously reported for glucose-induced activation of trehalase in glucose-depressed yeast cells. Further reduction of TPK-encoded catalytic subunit activity by partially inactivating point mutations in the remaining TPK gene further diminished nitrogen-induced trehalase activation, while deletion of the BCY1 gene (which encodes the regulatory subunit) in the same strains resulted in an increase in the extent of activation. Deletion of the RAS genes in such a tpkw1 bcy1 strain had no effect. These results are consistent with mediation of nitrogen-induced trehalase activation by the free catalytic subunits alone. They support our previous conclusion that cAMP does not act as second messenger in this nitrogen-induced activation process and our suggestion that a novel nitrogen-induced signaling pathway integrates with the cAMP pathway at the level of the free catalytic subunits of protein kinase A. Western blot experiments showed that the differences in the extent of trehalase activation were not due to differences in trehalase expression. On the other hand, we cannot completely exclude that protein kinase A influences the nitrogen-induced activation mechanism itself rather than acting directly on trehalase. However, any such alternative explanation requires the existence of an additional, yet unknown, mechanism for activation of trehalase besides the well-established regulation by protein kinase A.
Asunto(s)
Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Compuestos de Nitrógeno/farmacología , Saccharomyces cerevisiae/crecimiento & desarrollo , Trehalasa/metabolismo , Aminoácidos/farmacología , División Celular/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/genética , Activación Enzimática/efectos de los fármacos , Fermentación , Glucosa/metabolismo , Mutación , Fosforilación , Saccharomyces cerevisiae/enzimología , Proteínas ras/metabolismoRESUMEN
Addition of glucose or fructose to cells of the yeast Saccharomyces cerevisiae grown on a nonfermentable carbon source triggers within a few minutes posttranslational activation of trehalase, repression of the CTT1 (catalase) and SSA3 (Hsp70) genes, and induction of the ribosomal protein genes RPL1, RPL25 and RPS33. By using appropriate sugar kinase mutants, it was shown that rapid glucose- or fructose-induced activation of trehalase requires phosphorylation of the sugar. On the other hand, partial induction of RPL1, RPL25 and RPS33 as well as partial repression of CTT1 and SSA3 were observed in the absence of sugar phosphorylation. In glucose-grown nitrogen-starved yeast cells readdition of a nitrogen source triggers activation of trehalase in a glucose- or fructose-dependent way, but with no apparent requirements for phosphorylation of the sugar. Repression of CTT1 and SSA3 under the same conditions was also largely dependent on the presence of the sugar and also in these cases there was a strong effect when the sugar could not be phosphorylated. Nitrogen induction of RPL1, RPL25 and RPS33 was much less dependent on the presence of the sugar, and only phosphorylated sugar caused a further increase in expression. These results show that two glucose-dependent signalling pathways, which can be distinguished on the basis of their requirement for glucose phosphorylation, appear to be involved in activation of trehalase, repression of CTT1 and SSA3 and induction of ribosomal protein genes. They also show that nutrient-induced repression of CTT1 and SSA3 is not a response to improvement of the growth conditions because the addition of nonmetabolizable sugar does not ameliorate the growth conditions. Similarly, the upshift in ribosomal protein synthesis cannot be a response to increased availability of energy or biosynthetic capacity derived from glucose, but it is apparently triggered to a significant extent by specific detection of glucose as such.
Asunto(s)
Metabolismo de los Hidratos de Carbono , Glucosa/metabolismo , Saccharomyces cerevisiae/metabolismo , Carbono/metabolismo , Catalasa/genética , Activación Enzimática , Fermentación , Fructosa/metabolismo , Proteínas Fúngicas/genética , Genes Fúngicos , Proteínas HSP70 de Choque Térmico/genética , Mutación , Fosforilación , ARN de Hongos/genética , ARN de Hongos/metabolismo , Proteínas Ribosómicas/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Transducción de Señal , Trehalasa/metabolismoRESUMEN
Em sequencia a serie historica iniciada em 1968, com o objetivo de obter indicacoes sobre a evolucao da sifilis no Estado de Sao Paulo (Brasil), foi feito levantamento dos dados de 1972 a 1978 que mostrou que ao longo do tempo e apesar das oscilacoes, nao houve variacoes substanciais dos coeficientes de positividade das reacoes de Wasserman e VDRL em convocados apresentados no municipio de Sao Paulo. No interior do Estado o aumento dos valores dos coeficientes de 1973, invertendo a tendencia anteriormente observada, aproxima esses indices aos do municipio. O estudo da subamostra indicou a presenca de proporcoes maiores de positividade em convocados apresentados no municipio comparados com os apresentados no interior do Estado,independentes da naturalidade, o que poderia sugerir semelhancas com os quadros epidemiologicos descritos para os paises desenvolvidos. Entre convocados apresentados na capital observou-se maiores proporcoes de positividade nos convocados nascidos em outros Estados do pais, o que evidenciaria a presenca da doenca associada a pobreza ou ao subdesenvolvimento. Nesse sentido, foi chamada a atencao para as peculiaridades epidemiologicas das doencas em vista da singularidade das respectivas organizacoes sociais num dado momento historico
Asunto(s)
Sífilis , Serodiagnóstico de la Sífilis , BrasilRESUMEN
A maioria dos estudos com o SQ 14225(Squibb), um inibidor da enzima de conversao de angiotensina, foram feitos em animais e pacientes hipertensos. Tendo em vista a possibilidade de a droga ter uma acao farmacologica independente do seu efeito sobre a renina angiotensina, resolvemos estuda-la no seguinte protocolo experimental: Caes normais foram submetidos a uma expansao de 20% do espaco extracelular com solucao salina isotonica para inibir a atividade plasmatica do sistema renina, angiotensina, aldosteroma (S.R.A.A.).Nossas observacoes indicam que o SQ 14225 administrado a caes por via endovenosa, na dose de 7mg/kg e na vigencia de inibicao do S.R.A.A. por expansao com salina, apresentada uma acao hipotensora, assim como provoca proteinuria transitoria, provavelmente por aumentar a permeabilidade da membrana basal glomerular