ACE activity is modulated by the enzyme alpha-galactosidase A

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Item Type:	Article
Title:	ACE activity is modulated by the enzyme alpha-galactosidase A
Creators Name:	Batista, E.C., Carvalho, L.R., Casarini, D.E., Carmona, A.K., Dos Santos, E.L., da Silva, E.D., Dos Santos, R.A., Nakaie, C.R., Rojas, M.V., de Oliveira, S.M., Bader, M., D'Almeida, V., Martins, A.M., de Picoly Souza, K. and Pesquero, J.B.
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 (rhalpha-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 rhalpha-GalA infusion). Interestingly, 2 weeks later, ACE activity was significantly upregulated and the plasma levels of angiotensin II increased in the patients treated with rhalpha-GalA following the elevations of ACE activity. The same inhibitory effect on ACE activity was also observed in rats after rhalpha-GalA infusion. Furthermore, ACE activity in CHO cells transfected with the human ACE was inhibited dose and time-dependently by rhalpha-GalA. In vitro, the incubation of plasma from healthy volunteers with rhalpha-GalA significantly reduced ACE activity. Finally, rhalpha-GalA also inhibited ACE activity and released galactose residues from purified rabbit lung ACE dose-dependently. In summary, our results suggest that rhalpha-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 rhalpha-GalA.
Keywords:	ACE, Angiotensin, Biochemistry, Biology, Blood Pressure, Angiotensin I-Converting Enzyme, alpha-Galactosidase A, Fabry Disease, ACE Inhibitors, Animals, Rats
Source:	Journal of Molecular Medicine
ISSN:	0946-2716
Publisher:	Springer
Volume:	89
Number:	1
Page Range:	65-74
Date:	January 2011
Official Publication:	https://doi.org/10.1007/s00109-010-0686-2
PubMed:	View item in PubMed

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