A possible alternative mechanism of kinin generation in vivo by cathepsin L

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dc.contributor.authorPuzer, L.
dc.contributor.authorVercesi, J.
dc.contributor.authorAlves, MFM
dc.contributor.authorBarros, NMT
dc.contributor.authorAraujo, M. S.
dc.contributor.authorJuliano, M. A.
dc.contributor.authorReis, M. L.
dc.contributor.authorJuliano, L.
dc.contributor.authorCarmona, A. K.
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2016-01-24T12:37:58Z
dc.date.available2016-01-24T12:37:58Z
dc.date.issued2005-07-01
dc.description.abstractWe investigated the ability of cathepsin L to induce a hypotensive effect after intravenous injection in rats and correlated this decrease in blood pressure with kinin generation. Simultaneously with blood pressure decrease, we detected plasma kininogen depletion in the treated rats. the effect observed in vivo was abolished by preincubation of cathepsin L with the cysteine peptidase-specific inhibitor E-64 (11 mu m) or by previous administration of the bradykinin B-2 receptor antagonist JE049 (4 mg/kg). A potentiation of the hypotensive effect caused by cathepsin L was observed by previous administration of the angiotensin I-converting enzyme inhibitor captopril (5 mg/kg). in vitro studies indicated that cathepsin L excised bradykinin from the synthetic fluorogenic peptide Abz-MTSVIRRPPGFSPFRAPRV-NH2, based on the Met(375)-Val(393) sequence of rat kininogen (Abz=o-aminobenzoic acid). in conclusion, our data indicate that in vivo cathepsin L releases a kinin-related peptide, and in vitro experiments suggest that the kinin generated is bradykinin. Although it is well known that cysteine proteases are strongly inhibited by kininogen, cathepsin L could represent an alternative pathway for kinin production in pathological processes.en
dc.description.affiliationUNIFESP, Escola Paulista Med, Dept Biophys, BR-04044020 São Paulo, Brazil
dc.description.affiliationUSP, Fac Ciencias Farmaceut Ribeirao Preto, BR-14049900 São Paulo, Brazil
dc.description.affiliationUNIFESP, Escola Paulista Med, Dept Biochem, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUNIFESP, Escola Paulista Med, Dept Biophys, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUNIFESP, Escola Paulista Med, Dept Biochem, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent699-704
dc.identifierhttp://dx.doi.org/10.1515/BC.2005.081
dc.identifier.citationBiological Chemistry. Berlin: Walter de Gruyter & Co, v. 386, n. 7, p. 699-704, 2005.
dc.identifier.doi10.1515/BC.2005.081
dc.identifier.issn1431-6730
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/28382
dc.identifier.wosWOS:000230893100011
dc.language.isoeng
dc.publisherWalter de Gruyter & Co
dc.relation.ispartofBiological Chemistry
dc.rightsAcesso restrito
dc.subjectblood pressure decreaseen
dc.subjectbradykininen
dc.subjectcathepsinsen
dc.subjectinflammationen
dc.subjectkininen
dc.subjectkininogenen
dc.titleA possible alternative mechanism of kinin generation in vivo by cathepsin Len
dc.typeArtigo
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