RESUMO
Plasma kallikrein plays a role in coagulation, fibrinolysis and inflammation. Cathepsins B and L participate in (patho)physiological processes such as peptide antigen processing, tissue remodeling events, protein turnover in cells, hormone processing and tumor invasion. The present work analyzes the processing of prekallikrein/kallikrein by lysosomal cathepsins. Prekallikrein is not hydrolyzed by catB, and catL generates an inactive fragment of prekallikrein. Both kallikrein chains are hydrolyzed by catL and the light chain is mainly hydrolyzed by catB; kallikrein activity is lower after incubation with catL compared to catB. Our data suggest that the plasma kallikrein/ kinin system can be controlled by cathepsins.
Assuntos
Catepsinas/metabolismo , Calicreínas/sangue , Lisossomos/enzimologia , Pré-Calicreína/metabolismo , Eletroforese em Gel de Poliacrilamida , HidróliseRESUMO
We investigated the influence of pH and divalent cations (Zn2+, Mg2+ and Ca2+) on high molecular weight kininogen processing by cathepsin B. At pH 6.3, high molecular weight kininogen is hydrolyzed by cathepsin B at three sites generating fragments of 80, 60 and 40 kDa. Cathepsin B has kininogenase activity at this pH which is improved in the absence of divalent cations. At pH 7.35, high molecular weight kininogen is slightly cleaved by cathepsin B into fragments of 60 kDa, and cathepsin B kininogenase activity is impaired. Our results suggest that high molecular weight kininogen is a substrate for cathepsin B under pathophysiological conditions.