ACE activity is modulated by the enzyme alpha-galactosidase A

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dc.contributor.authorBatista, Elice Carneiro
dc.contributor.authorCarvalho, Luiz Roberto
dc.contributor.authorCasarini, Dulce Elena [UNIFESP]
dc.contributor.authorCarmona, Adriana Karaoglanovic
dc.contributor.authorSantos, Edson Lucas dos
dc.contributor.authorSilva, Elton Dias da
dc.contributor.authorSantos, Robson Augusto dos
dc.contributor.authorNakaie, Clovis Ryuichi
dc.contributor.authorMunoz Rojas, Maria Veronica
dc.contributor.authorOliveira, Suzana Macedo de
dc.contributor.authorBader, Michael
dc.contributor.authorD'Almeida, Vania [UNIFESP]
dc.contributor.authorMartins, Ana Maria [UNIFESP]
dc.contributor.authorSouza, Kely de Picoly
dc.contributor.authorPesquero, Joao Bosco [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionMax Delbruck Ctr Mol Med MDC
dc.contributor.institutionGenzyme Brasil
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionFed Univ Grande Dourados
dc.contributor.institutionHosp Sao Vicente de Paulo
dc.date.accessioned2016-01-24T14:05:56Z
dc.date.available2016-01-24T14:05:56Z
dc.date.issued2011-01-01
dc.description.abstractFabry disease is a multisystem X-linked disorder resulting from alpha-galactosidase A (alpha-GalA) gene mutations leading to the accumulation of globotriaosylceramide mainly in endothelium compromising heart, kidney, and brain. in Fabry patients, progressive renal failure is frequently treated with angiotensin I-converting enzyme (ACE) inhibitors. We were interested in the possible interactions between ACE inhibitors therapy and the only causative therapy for Fabry disease, the enzyme replacement therapy (ERT) using recombinant human alpha-GalA (rh alpha-GalA). Our results suggest that ACE activity was significantly inhibited in plasma of Fabry patients and the blood pressure level decreased just after ERT (at the end of the rh alpha-GalA infusion). Interestingly, 2 weeks later, ACE activity was significantly upregulated and the plasma levels of angiotensin II increased in the patients treated with rh alpha-GalA following the elevations of ACE activity. the same inhibitory effect on ACE activity was also observed in rats after rh alpha-GalA infusion. Furthermore, ACE activity in CHO cells transfected with the human ACE was inhibited dose and time-dependently by rh alpha-GalA. in vitro, the incubation of plasma from healthy volunteers with rh alpha-GalA significantly reduced ACE activity. Finally, rh alpha-GalA also inhibited ACE activity and released galactose residues from purified rabbit lung ACE dose-dependently. in summary, our results suggest that rh alpha-GalA interacts with ACE and inhibits its activity, possibly by removing the galactose residues from the enzyme. This modulation might have profound impact on the clinical outcome of Fabry patients treated with rh alpha-GalA.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, BR-04023062 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Pediat, BR-04023062 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biosci, BR-04023062 São Paulo, Brazil
dc.description.affiliationMax Delbruck Ctr Mol Med MDC, D-13125 Berlin, Germany
dc.description.affiliationGenzyme Brasil, Personalized Genet Hlth, São Paulo, Brazil
dc.description.affiliationUniv Fed Minas Gerais, Dept Physiol & Biophys, Belo Horizonte, MG, Brazil
dc.description.affiliationFed Univ Grande Dourados, Sch Environm & Biol Sci, Dourados, MS, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Med, Div Nephrol, BR-04023062 São Paulo, Brazil
dc.description.affiliationHosp Sao Vicente de Paulo, Dept Nephrol, Passo Fundo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Pediat, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biosci, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Med, Div Nephrol, BR-04023062 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipDeutsche Akademische Austauschdienst (DAAD/PROBRAL)
dc.description.sponsorshipDeutsche Forschungsgemeinschaft
dc.description.sponsorshipIDFAPESP: 2008/06676-8
dc.description.sponsorshipIDCAPES: 239/06
dc.description.sponsorshipIDDeutsche Forschungsgemeinschaft: BA 1374/16-1
dc.description.sponsorshipIDCAPES: 33009015001
dc.format.extent65-74
dc.identifierhttp://dx.doi.org/10.1007/s00109-010-0686-2
dc.identifier.citationJournal of Molecular Medicine-jmm. New York: Springer, v. 89, n. 1, p. 65-74, 2011.
dc.identifier.doi10.1007/s00109-010-0686-2
dc.identifier.issn0946-2716
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33260
dc.identifier.wosWOS:000288363200008
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofJournal of Molecular Medicine-jmm
dc.rightsAcesso restrito
dc.rights.licensehttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.subjectACEen
dc.subjectAngiotensinen
dc.subjectBiochemistryen
dc.subjectBiologyen
dc.subjectBlood pressureen
dc.subjectAngiotensin I-converting enzyme alpha-galactosidase Aen
dc.subjectFabry diseaseen
dc.subjectACE inhibitorsen
dc.titleACE activity is modulated by the enzyme alpha-galactosidase Aen
dc.typeArtigo
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