ACE activity is modulated by the enzyme alpha-galactosidase A

ACE activity is modulated by the enzyme alpha-galactosidase A

Author Batista, Elice Carneiro Google Scholar
Carvalho, Luiz Roberto Google Scholar
Casarini, Dulce Elena Autor UNIFESP Google Scholar
Carmona, Adriana Karaoglanovic Google Scholar
Santos, Edson Lucas dos Google Scholar
Silva, Elton Dias da Google Scholar
Santos, Robson Augusto dos Google Scholar
Nakaie, Clovis Ryuichi Google Scholar
Munoz Rojas, Maria Veronica Google Scholar
Oliveira, Suzana Macedo de Google Scholar
Bader, Michael Google Scholar
D'Almeida, Vania Autor UNIFESP Google Scholar
Martins, Ana Maria Autor UNIFESP Google Scholar
Souza, Kely de Picoly Google Scholar
Pesquero, Joao Bosco Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Max Delbruck Ctr Mol Med MDC
Genzyme Brasil
Universidade Federal de Minas Gerais (UFMG)
Fed Univ Grande Dourados
Hosp Sao Vicente de Paulo
Abstract Fabry 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.
Keywords ACE
Blood pressure
Angiotensin I-converting enzyme alpha-galactosidase A
Fabry disease
ACE inhibitors
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Deutsche Akademische Austauschdienst (DAAD/PROBRAL)
Deutsche Forschungsgemeinschaft
Grant number FAPESP: 2008/06676-8
CAPES: 239/06
Deutsche Forschungsgemeinschaft: BA 1374/16-1
CAPES: 33009015001
Date 2011-01-01
Published in Journal of Molecular Medicine-jmm. New York: Springer, v. 89, n. 1, p. 65-74, 2011.
ISSN 0946-2716 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 65-74
Access rights Closed access
Type Article
Web of Science ID WOS:000288363200008

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