Document Detail


Pharmacological and genetic evidence that cathepsin B is not the physiological activator of rodent prorenin.
MedLine Citation:
PMID:  20868234     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Renin is the first enzyme in the renin-angiotensin-aldosterone system which is the principal regulator of blood pressure and hydroelectrolyte balance. Previous studies suggest that cathepsin B is the activator of the prorenin zymogen. Here, we show no difference in plasma renin activity, or mean arterial blood pressure between wild-type and cathepsin B knockout mice. To account for potential gene compensation, a potent, selective, reversible cathepsin B inhibitor was developed to determine the role of cathepsin B on prorenin processing in rats. Pharmacological inhibition of cathepsin B in spontaneously hypertensive and double transgenic rats did not result in a reduction in renal mature renin protein levels or plasma renin activity. We conclude that cathepsin B does not play a significant role in this process in rodents.
Authors:
M David Percival; Sylvie Toulmond; Nathalie Coulombe; Wanda Cromlish; Sylvie Desmarais; Susana Liu; René St-Jacques; Jacques Yves Gauthier; Jean-Francois Fournier
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological chemistry     Volume:  391     ISSN:  1437-4315     ISO Abbreviation:  Biol. Chem.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-03-14     Revised Date:  2012-09-17    
Medline Journal Info:
Nlm Unique ID:  9700112     Medline TA:  Biol Chem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1469-73     Citation Subset:  IM    
Affiliation:
Department of In Vitro Sciences, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada. dave_percival@merck.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Cathepsin B / antagonists & inhibitors,  genetics,  physiology*
Enzyme Inhibitors / pharmacology
Hypertension / genetics,  metabolism
Mice
Mice, Knockout
Rats
Rats, Transgenic
Renin / metabolism*
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; EC 3.4.22.1/Cathepsin B; EC 3.4.23.15/Renin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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