T-kininogen inhibits kinin-mediated activation of ERK in endothelial cells

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 cyst...

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Main Authors:	LEIVA-SALCEDO,ELIAS, PEREZ,VIVIANA, ACUÑA-CASTILLO,CLAUDIO, WALTER,ROBIN, SIERRA,FELIPE
Language:	English
Published:	Sociedad de Biología de Chile 2002
Subjects:	aging endothelial cells ERK pathway kininogen kinins
Online Access:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200020
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spelling	oai:scielo:S0716-976020020002000202002-12-26T-kininogen inhibits kinin-mediated activation of ERK in endothelial cellsLEIVA-SALCEDO,ELIASPEREZ,VIVIANAACUÑA-CASTILLO,CLAUDIOWALTER,ROBINSIERRA,FELIPE aging endothelial cells ERK pathway kininogen kinins 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 vivoinfo:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.35 n.2 20022002-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200020en10.4067/S0716-97602002000200020
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	aging endothelial cells ERK pathway kininogen kinins
spellingShingle	aging endothelial cells ERK pathway kininogen kinins LEIVA-SALCEDO,ELIAS PEREZ,VIVIANA ACUÑA-CASTILLO,CLAUDIO WALTER,ROBIN SIERRA,FELIPE T-kininogen inhibits kinin-mediated activation of ERK in endothelial cells
description	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
author	LEIVA-SALCEDO,ELIAS PEREZ,VIVIANA ACUÑA-CASTILLO,CLAUDIO WALTER,ROBIN SIERRA,FELIPE
author_facet	LEIVA-SALCEDO,ELIAS PEREZ,VIVIANA ACUÑA-CASTILLO,CLAUDIO WALTER,ROBIN SIERRA,FELIPE
author_sort	LEIVA-SALCEDO,ELIAS
title	T-kininogen inhibits kinin-mediated activation of ERK in endothelial cells
title_short	T-kininogen inhibits kinin-mediated activation of ERK in endothelial cells
title_full	T-kininogen inhibits kinin-mediated activation of ERK in endothelial cells
title_fullStr	T-kininogen inhibits kinin-mediated activation of ERK in endothelial cells
title_full_unstemmed	T-kininogen inhibits kinin-mediated activation of ERK in endothelial cells
title_sort	t-kininogen inhibits kinin-mediated activation of erk in endothelial cells
publisher	Sociedad de Biología de Chile
publishDate	2002
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602002000200020
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T-kininogen inhibits kinin-mediated activation of ERK in endothelial cells

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