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dc.contributor.authorDanilov, Sergei M.*
dc.contributor.authorLünsdorf, Heinrich*
dc.contributor.authorAkinbi, Henry T.*
dc.contributor.authorNesterovitch, Andrew B.*
dc.contributor.authorEpshtein, Yuliya*
dc.contributor.authorLetsiou, Eleftheria*
dc.contributor.authorKryukova, Olga V.*
dc.contributor.authorPiegeler, Tobias*
dc.contributor.authorGolukhova, Elena Z.*
dc.contributor.authorSchwartz, David E.*
dc.contributor.authorDull, Randal O.*
dc.contributor.authorMinshall, Richard D.*
dc.contributor.authorKost, Olga A.*
dc.contributor.authorGarcia, Joe G. N.*
dc.date.accessioned2017-01-12T21:19:15Z
dc.date.available2017-01-12T21:19:15Z
dc.date.issued2016-10-13
dc.identifier.citationLysozyme and bilirubin bind to ACE and regulate its conformation and shedding 2016, 6:34913 Scientific Reportsen
dc.identifier.issn2045-2322
dc.identifier.pmid27734897
dc.identifier.doi10.1038/srep34913
dc.identifier.urihttp://hdl.handle.net/10150/621944
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.
dc.description.sponsorshipMinistry of Science and Education of Russian Federation [14.Z50.31.0026]en
dc.language.isoenen
dc.publisherNATURE PUBLISHING GROUPen
dc.relation.urlhttp://www.nature.com/articles/srep34913en
dc.rights© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License.en
dc.titleLysozyme and bilirubin bind to ACE and regulate its conformation and sheddingen
dc.typeArticleen
dc.contributor.departmentUniv Arizona Hlth Scien
dc.identifier.journalScientific Reportsen
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
refterms.dateFOA2018-04-26T12:02:07Z
html.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.


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