Navegando por Palavras-chave "Calicreína Plasmática"

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    Ação De Calicreína Plasmática Humana Sobre A Resposta Da Agregação Plaquetária Induzida Por Doses Hipoagregantes De Adp
    (Universidade Federal de São Paulo (UNIFESP), 2017-09-28) Fontes, Tatiana Neves [UNIFESP]; Oliva, Maria Luiza Vilela [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Human plasma kallikreín (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not índuce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets , potentiates ADP-induced platelet actívation by prior proteolysis of the G-proteincoupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin allb~3 through interactions with the KGD/KGE sequence motif ín huPK. Integrin allbf33 is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway. This activation pathway leads to phosphorylation of Src, AktS473, ERK1/2, and p38 MAPK, and to Ca2+ release. The effect of huPK is blocked by specific antagonists of PAR-1 (SCH 19197) and allb~3 (abciximab) and by synthetic peptides comprising the KGD and KGE sequence motifs of huPK. Further, recombinant plasma kallikrein ínhibítor, rBbKI, also blocks this entíre mechanism. These results suggest a new function for huPK. Formation of plasma kallikrein lowers the threshold for ADP~induced platelet activation. The present observatíons are consistent wíth the notion that plasma kallikrein promotes vascu!ar disease and thrombosis in the intravascular compartment.