%0 Journal Article
%T T-kininogen inhibits kinin-mediated activation of ERK in endothelial cells
%A LEIVA-SALCEDO
%A ELIAS
%A PEREZ
%A VIVIANA
%A ACU£¿A-CASTILLO
%A CLAUDIO
%A WALTER
%A ROBIN
%A SIERRA
%A FELIPE
%J Biological Research
%D 2002
%I Sociedad de Biolog¨ªa de Chile
%R 10.4067/S0716-97602002000200020
%X serum levels of t-kininogen increase dramatically as rats approach the end of their lifespan. stable expression of the protein in balb/c 3t3 fibroblasts leads to a dramatic inhibition of cell proliferation, as well as inhibition of the erk signaling pathway. t-kininogen is a potent inhibitor of cysteine proteinases, and we have described that the inhibition of erk activity occurs, at least in part, via stabilization of the map kinase phosphatase, mkp-1. since fibroblasts are not a physiological target of t-kininogen, we have now purified the protein from rat serum, and used it to assess the effect of t-kininogen on endothelial cells. adding purified t-kininogen to eahy 926 hybridoma cells resulted in inhibition of basal erk activity levels, as estimated using appropriate anti-phospho erk antibodies. furthermore, exogenously added t-kininogen inhibited the activation of the erk pathway induced by either bradykinin or t-kinin. we conclude that the age-related increase in hepatic t-kininogen gene expression and serum levels of the protein could have dramatic consequences on endothelial cell physiology, both under steady state conditions, and after activation by cell-specific stimuli. our results are consistent with t-kininogen being an important modulator of the senescent phenotype in vivo
%K aging
%K endothelial cells
%K erk pathway
%K kininogen
%K kinins.
%U http://www.scielo.cl/scielo.php?script=sci_abstract&pid=S0716-97602002000200020&lng=en&nrm=iso&tlng=en