Document Detail


Network Modeling Reveals Steps in Angiotensin Peptide Processing.
MedLine Citation:
PMID:  23283355     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
New insights into the intrarenal renin-angiotensin (Ang) system have modified our traditional view of the system. However, many finer details of this network of peptides and associated peptidases remain unclear. We hypothesized that a computational systems biology approach, applied to peptidomic data, could help to unravel the network of enzymatic conversions. We built and refined a Bayesian network model and a dynamic systems model starting from a skeleton created with established elements of the renin-Ang system and further developed it with archived matrix-assisted laser desorption ionization-time of flight mass spectra from experiments conducted in mouse podocytes exposed to exogenous Ang substrates. The model-building process suggested previously unrecognized steps, 3 of which were confirmed in vitro, including the conversion of Ang(2-10) to Ang(2-7) by neprilysin, Ang(1-9) to Ang(2-9), and Ang(1-7) to Ang(2-7) by aminopeptidase A. These data suggest a wider role of neprilysin and aminopeptidase A in glomerular formation of bioactive Ang peptides and shunting their formation. Other steps were also suggested by the model, and supporting evidence for those steps was evaluated using model-comparison methods. Our results demonstrate that systems biology methods applied to peptidomic data are effective in identifying novel steps in the Ang peptide processing network, and these findings improve our understanding of the glomerular renin-Ang system.
Authors:
John H Schwacke; John Christian G Spainhour; Jessalyn L Ierardi; Jose M Chaves; John M Arthur; Michael G Janech; Juan Carlos Q Velez
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-2
Journal Detail:
Title:  Hypertension     Volume:  -     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Biochemistry and Molecular Biology and Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC; and Medical and Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC.
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