RGD Reference Report - ACE activity is modulated by the enzyme a-galactosidase A. - Rat Genome Database

Send us a Message

Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

ACE activity is modulated by the enzyme a-galactosidase A.

Authors: Batista, Elice Carneiro  Carvalho, Luiz Roberto  Casarini, Dulce Elena  Carmona, Adriana Karaoglanovic  dos Santos, Edson Lucas  da Silva, Elton Dias  dos Santos, Robson Augusto  Nakaie, Clovis Ryuichi  Rojas, Maria Verônica Munoz  de Oliveira, Suzana Macedo  Bader, Michael  D'Almeida, Vânia  Martins, Ana Maria  de Picoly Souza, Kely  Pesquero, João Bosco 
Citation: Batista EC, etal., J Mol Med (Berl). 2011 Jan;89(1):65-74. doi: 10.1007/s00109-010-0686-2. Epub 2010 Oct 13.
RGD ID: 12879402
Pubmed: (View Article at PubMed) PMID:20941593
DOI: Full-text: DOI:10.1007/s00109-010-0686-2

Fabry disease is a multisystem X-linked disorder resulting from α-galactosidase A (α-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 α-GalA (rhα-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 rhα-GalA infusion). Interestingly, 2 weeks later, ACE activity was significantly upregulated and the plasma levels of angiotensin II increased in the patients treated with rhα-GalA following the elevations of ACE activity. The same inhibitory effect on ACE activity was also observed in rats after rhα-GalA infusion. Furthermore, ACE activity in CHO cells transfected with the human ACE was inhibited dose and time-dependently by rhα-GalA. In vitro, the incubation of plasma from healthy volunteers with rhα-GalA significantly reduced ACE activity. Finally, rhα-GalA also inhibited ACE activity and released galactose residues from purified rabbit lung ACE dose-dependently. In summary, our results suggest that rhα-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 rhα-GalA.


Disease Annotations    
Fabry disease  (IDA,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Ace  (angiotensin I converting enzyme)

Genes (Mus musculus)
Ace  (angiotensin I converting enzyme (peptidyl-dipeptidase A) 1)

Genes (Homo sapiens)
ACE  (angiotensin I converting enzyme)

Additional Information