Heparan sulfate modulates kinin release by Trypanosoma cruzi through the activity of cruzipain

Heparan sulfate modulates kinin release by Trypanosoma cruzi through the activity of cruzipain

Author Lima, APCA Google Scholar
Almeida, P. C. Google Scholar
Tersariol, Ivarne Luis dos Santos Autor UNIFESP Google Scholar
Schmitz, V Google Scholar
Schmaier, A. H. Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Hirata, Izaura Yoshico Autor UNIFESP Google Scholar
Muller-Esterl, W. Google Scholar
Chagas, Jair Ribeiro Autor UNIFESP Google Scholar
Scharfstein, J. Google Scholar
Institution Univ Brazil
Univ Mogi Cruzes
Universidade Federal de São Paulo (UNIFESP)
Univ Michigan
Univ Frankfurt
Abstract Trypanosoma cruzi activates the kinin pathway through the activity of its major cysteine proteinase, cruzipain. Because kininogen molecules may be displayed on cell surfaces by binding to glycosaminoglycans, we examined whether the ability of cruzipain to release kinins from high molecular weight kininogen (HK) is modulated by heparan sulfate (HS). Kinetic assays show that HS reduces the cysteine proteinase inhibitory activity (K-i (app)) of HK about 10-fold. Conversely, the catalytic efficiency of cruzipain on kinin-related synthetic fluorogenic substrates is enhanced up to 6-fold in the presence of HS. Analysis of the HK breakdown products generated by cruzipain indicated that HS changes the pattern of HK cleavage products. Direct measurements of bradykinin demonstrated an up to 35-fold increase in cruzipain-mediated kinin liberation in the presence of HS. Similarly, kinin release by living trypomastigotes increased up to 10-fold in the presence of HS. These studies suggest that the efficiency of T. cruzi to initiate kinin release is potently enhanced by the mutual interactions between cruzipain, HK, and heparan sulfate proteoglyeans.
Language English
Date 2002-02-22
Published in Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 277, n. 8, p. 5875-5881, 2002.
ISSN 0021-9258 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Biochemistry Molecular Biology Inc
Extent 5875-5881
Origin http://dx.doi.org/10.1074/jbc.M108518200
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000173989200025
URI http://repositorio.unifesp.br/handle/11600/26758

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