Please use this identifier to cite or link to this item: http://repositorio.unifesp.br/handle/11600/26758
Title: Heparan sulfate modulates kinin release by Trypanosoma cruzi through the activity of cruzipain
Authors: Lima, APCA
Almeida, P. C.
Tersariol, Ivarne Luis dos Santos [UNIFESP]
Schmitz, V
Schmaier, A. H.
Juliano, Luiz [UNIFESP]
Hirata, Izaura Yoshico [UNIFESP]
Muller-Esterl, W.
Chagas, Jair Ribeiro [UNIFESP]
Scharfstein, J.
Univ Brazil
Univ Mogi Cruzes
Universidade Federal de São Paulo (UNIFESP)
Univ Michigan
Univ Frankfurt
Issue Date: 22-Feb-2002
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Citation: Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 277, n. 8, p. 5875-5881, 2002.
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.
URI: http://repositorio.unifesp.br/handle/11600/26758
ISSN: 0021-9258
Other Identifiers: http://dx.doi.org/10.1074/jbc.M108518200
Appears in Collections:Em verificação - Geral

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