ACE phenotyping in Gaucher disease

Molecular Genetics and Metabolism
Sergei M DanilovEllen Sidransky

Abstract

Gaucher disease is characterized by the activation of splenic and hepatic macrophages, accompanied by dramatically increased levels of angiotensin-converting enzyme (ACE). To evaluate the source of the elevated blood ACE, we performed complete ACE phenotyping using blood, spleen and liver samples from patients with Gaucher disease and controls. ACE phenotyping included 1) immunohistochemical staining for ACE; 2) measuring ACE activity with two substrates (HHL and ZPHL); 3) calculating the ratio of the rates of substrate hydrolysis (ZPHL/HHL ratio); 4) assessing the conformational fingerprint of ACE by evaluating the pattern of binding of monoclonal antibodies to 16 different ACE epitopes. We show that in patients with Gaucher disease, the dramatically increased levels of ACE originate from activated splenic and/or hepatic macrophages (Gaucher cells), and that both its conformational fingerprint and kinetic characteristics (ZPHL/HHL ratio) differ from controls and from patients with sarcoid granulomas. Furthermore, normal spleen was found to produce high levels of endogenous ACE inhibitors and a novel, tightly-bound 10-30 kDa ACE effector which is deficient in Gaucher spleen. The conformation of ACE is tissue-specific. In Gauche...Continue Reading

Citations

Dec 28, 2018·PloS One·Sergei M DanilovOlga A Kost
Dec 27, 2019·PloS One·Sergei M DanilovJoe G N Garcia
Dec 25, 2019·The Journal of Biological Chemistry·Duo-Yao CaoKenneth E Bernstein
Nov 7, 2019·Oncotarget·Sergei M DanilovArmais A Kamalov
Jul 14, 2020·Internal Medicine Journal·Ari ZimranShoshana Revel-Vilk
May 1, 2021·European Respiratory Review : an Official Journal of the European Respiratory Society·Raphaël BorieOlivier Lidove
May 2, 2021·Protein Science : a Publication of the Protein Society·Isolda A PopovaSergei M Danilov
Nov 4, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Vatsala Khurana, Binita Goswami

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