2.50
Hdl Handle:
http://hdl.handle.net/10033/620587
Title:
Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding.
Authors:
Danilov, Sergei M; Lünsdorf, 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
Abstract:
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding. 2016, 6:34913 Sci Rep
Journal:
Scientific reports
Issue Date:
13-Oct-2016
URI:
http://hdl.handle.net/10033/620587
DOI:
10.1038/srep34913
PubMed ID:
27734897
Type:
Article
ISSN:
2045-2322
Appears in Collections:
publications of the central unit for microscopy (ZEIM)

Full metadata record

DC FieldValue Language
dc.contributor.authorDanilov, Sergei Men
dc.contributor.authorLünsdorf, Heinrichen
dc.contributor.authorAkinbi, Henry Ten
dc.contributor.authorNesterovitch, Andrew Ben
dc.contributor.authorEpshtein, Yuliyaen
dc.contributor.authorLetsiou, Eleftheriaen
dc.contributor.authorKryukova, Olga Ven
dc.contributor.authorPiegeler, Tobiasen
dc.contributor.authorGolukhova, Elena Zen
dc.contributor.authorSchwartz, David Een
dc.contributor.authorDull, Randal Oen
dc.contributor.authorMinshall, Richard Den
dc.contributor.authorKost, Olga Aen
dc.contributor.authorGarcia, Joe G Nen
dc.date.accessioned2016-11-18T10:20:16Z-
dc.date.available2016-11-18T10:20:16Z-
dc.date.issued2016-10-13-
dc.identifier.citationLysozyme and bilirubin bind to ACE and regulate its conformation and shedding. 2016, 6:34913 Sci Repen
dc.identifier.issn2045-2322-
dc.identifier.pmid27734897-
dc.identifier.doi10.1038/srep34913-
dc.identifier.urihttp://hdl.handle.net/10033/620587-
dc.description.abstractAngiotensin 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.en
dc.languageENG-
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleLysozyme and bilirubin bind to ACE and regulate its conformation and shedding.
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalScientific reportsen

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