Tissue specificity of human angiotensin I-converting enzyme

Olga V. Kryukova, Victoria E. Tikhomirova, Elena Z. Golukhova, Valery V. Evdokimov, Gavreel F. Kalantarov, Ilya N. Trakht, David E. Schwartz, Randal O. Dull, Alexander V. Gusakov, Igor V. Uporov, Olga A. Kost, Sergei M. Danilov

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background: Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in reproductive functions, is expressed as a type-1 membrane glycoprotein on the surface of endothelial and epithelial cells. ACE also presents as a soluble form in biological fluids, among which seminal fluid being the richest in ACE content - 50-fold more than that in blood. Methods/Principal Findings: We performed conformational fingerprinting of lung and seminal fluid ACEs using a set of monoclonal antibodies (mAbs) to 17 epitopes of human ACE and determined the effects of potential ACE-binding partners on mAbs binding to these two different ACEs. Patterns of mAbs binding to ACEs from lung and from seminal fluid dramatically differed, which reflects difference in the local conformations of these ACEs, likely due to different patterns of ACE glycosylation in the lung endothelial cells and epithelial cells of epididymis/prostate (source of seminal fluid ACE), confirmed by mass-spectrometry of ACEs tryptic digests. Conclusions: Dramatic differences in the local conformations of seminal fluid and lung ACEs, as well as the effects of ACE-binding partners on mAbs binding to these ACEs, suggest different regulation of ACE functions and shedding from epithelial cells in epididymis and prostate and endothelial cells of lung capillaries. The differences in local conformation of ACE could be the base for the generation of mAbs distingushing tissue-specific ACEs.

Original languageEnglish (US)
Article numbere0143455
JournalPloS one
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Kryukova, O. V., Tikhomirova, V. E., Golukhova, E. Z., Evdokimov, V. V., Kalantarov, G. F., Trakht, I. N., Schwartz, D. E., Dull, R. O., Gusakov, A. V., Uporov, I. V., Kost, O. A., & Danilov, S. M. (2015). Tissue specificity of human angiotensin I-converting enzyme. PloS one, 10(11), [e0143455]. https://doi.org/10.1371/journal.pone.0143455