Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding.
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Authors
Danilov, Sergei MLünsdorf, Heinrich
Akinbi, Henry T
Nesterovitch, Andrew B
Epshtein, Yuliya
Letsiou, Eleftheria
Kryukova, Olga V
Piegeler, Tobias
Golukhova, Elena Z
Schwartz, David E
Dull, Randal O
Minshall, Richard D
Kost, Olga A
Garcia, Joe G N
Issue Date
2016-10-13
Metadata
Show full item recordAbstract
Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients.Citation
Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding. 2016, 6:34913 Sci RepAffiliation
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.Journal
Scientific reportsPubMed ID
27734897Type
ArticleISSN
2045-2322ae974a485f413a2113503eed53cd6c53
10.1038/srep34913
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
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