Involvement of heparan sulfate proteoglycans in cellular uptake of high molecular weight kininogen

Involvement of heparan sulfate proteoglycans in cellular uptake of high molecular weight kininogen

Author Melo, Katia R. B. Autor UNIFESP Google Scholar
Gutierrez, Augusto Autor UNIFESP Google Scholar
Nascimento, Fabio D. Autor UNIFESP Google Scholar
Araujo, Mariana S. Autor UNIFESP Google Scholar
Sampaio, Misako U. Autor UNIFESP Google Scholar
Carmona, Adriana K. Autor UNIFESP Google Scholar
Coulson-Thomas, Yvette May Autor UNIFESP Google Scholar
Trindade, Edvaldo S. Autor UNIFESP Google Scholar
Nader, Helena B. Autor UNIFESP Google Scholar
Tersariol, Ivarne L. S. Autor UNIFESP Google Scholar
Motta, Guacyara Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Fed Parana
Univ Mogi das Cruzes
Abstract In this study, we analyzed the influence of proteoglycans on the interaction between human high molecular weight kininogen (HK) and the cell surface. We found that D5-related peptide inhibits HK-biotin cellular uptake. Confocal microscopy showed that HK colocalizes with heparan sulfate proteoglycan (HSPG) at the cell surface. When biotin-HK is incubated with rabbit aorta endothelial cells (RAECs) and CHO-K1 cells, it is internalized into acidic intracellular vesicles, whereas when incubated with CHO-745 cells, which express reduced levels of glycosaminoglycans, HK is not internalized. To further verify the hypothesis that HSPG-dependent mechanisms are involved in HK uptake and proteolytic processing in lysosomes, we tested chloroquine, which blocks Alexa 488-HK colocalization with Lyso Tracker in acidic endosomal vesicles. the process of HK internalization was blocked by low temperatures, methyl-beta-cyclodextrin, FCCP and 2-deoxy-D-glucose, implying that HK uptake into acidic vesicles is energy-dependent and most likely involves binding to HSPG structures localized in cholesterol-rich domains present in the plasma membrane. Kinin generation at the cell surface was much higher in tumorigenic cells (CHO-K1) when compared to endothelial cells (RAECs). the present data indicate that the process of HK endocytosis involving HSPG is a novel additional mechanism which may control kinin generation at the cell surface.
Keywords endocytosis
endothelial cells
glycosaminoglycans
kinin release
proteolysis
tumor cells
Language English
Sponsor Fundacao de Amparo a Pesquisa do, Estado de São Paulo
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundo de Auxilio aos Docentes e Alunos-FADA/UNIFESP
Department of Biochemistry, UNIFESP
Grant number Fundacao de Amparo a Pesquisa do, Estado de São Paulo: FAPESP 02/09808-6
Fundacao de Amparo a Pesquisa do, Estado de São Paulo: PRONEX-FAPESP 03/10516-2
CNPq: CNPq 472403/2007-9
Date 2009-02-01
Published in Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 390, n. 2, p. 145-155, 2009.
ISSN 1431-6730 (Sherpa/Romeo, impact factor)
Publisher Walter de Gruyter & Co
Extent 145-155
Origin http://dx.doi.org/10.1515/BC.2009.016
Access rights Closed access
Type Article
Web of Science ID WOS:000263657700007
URI http://repositorio.unifesp.br/handle/11600/31314

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