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dc.creatorLEIVA-SALCEDO,ELIAS
dc.creatorPEREZ,VIVIANA
dc.creatorACUÑA-CASTILLO,CLAUDIO
dc.creatorWALTER,ROBIN
dc.creatorSIERRA,FELIPE
dc.date2002-01-01
dc.date.accessioned2019-09-10T12:42:15Z
dc.date.available2019-09-10T12:42:15Z
dc.identifierhttps://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200020
dc.identifier.urihttps://revistaschilenas.uchile.cl/handle/2250/107005
dc.descriptionSerum 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
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dc.languageen
dc.publisherSociedad de Biología de Chile
dc.relation10.4067/S0716-97602002000200020
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourceBiological Research v.35 n.2 2002
dc.subjectaging
dc.subjectendothelial cells
dc.subjectERK pathway
dc.subjectkininogen
dc.subjectkinins
dc.titleT-kininogen inhibits kinin-mediated activation of ERK in endothelial cells


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