Document Detail


Pharmacological inhibition of excessive collagen deposition in fibrotic diseases.
MedLine Citation:
PMID:  6479355     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Excessive accumulation of collagen is a major pathological feature in diseases characterized by tissue fibrosis. Although several therapeutic approaches have been attempted in such patients, currently no treatment modality would specifically reduce collagen deposition in tissues. In this paper we discuss the mode of action of compounds that interfere with collagen production on the posttranslational level. First, structural analogs of proline, cis-4-hydroxy-L-proline and L-azetidine-2-carboxylic acid, which are incorporated into the newly synthesized polypeptides of procollagen during translation, prevent the polypeptides from folding into a stable triple-helical conformation. As a consequence, the nonhelical polypeptides are subject to degradation by proteases, thus leading to reduced deposition of collagen fibers. Second, several naturally occurring amino acids, polyamines, and their structural analogs prevent the removal of the carboxy-terminal extensions during the extracellular conversion of procollagen to collagen. Because the precursor molecules that contain the carboxy-terminal extensions are unable to assemble into functional fibers, collagen deposition is again reduced. Further development of these and related compounds, with appropriate tissue targeting, could potentially provide us with novel means to reduce the excessive deposition of collagen in fibrotic processes.
Authors:
J Uitto; L Ryhänen; E M Tan; A I Oikarinen; E J Zaragoza
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Federation proceedings     Volume:  43     ISSN:  0014-9446     ISO Abbreviation:  Fed. Proc.     Publication Date:  1984 Oct 
Date Detail:
Created Date:  1984-11-05     Completed Date:  1984-11-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372771     Medline TA:  Fed Proc     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2815-20     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Azetidinecarboxylic Acid / pharmacology
Cell Division / drug effects
Cells, Cultured
Chick Embryo
Collagen / biosynthesis,  metabolism*
Fibroblasts / drug effects
Humans
Nucleic Acid Hybridization
Polyamines / pharmacology
Procollagen / metabolism
Proline / analogs & derivatives*
Protein Conformation
Protein Processing, Post-Translational / drug effects
Sclerosis / metabolism
Grant Support
ID/Acronym/Agency:
AG-03172/AG/NIA NIH HHS; AM-28450/AM/NIADDK NIH HHS; GM-28833/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Polyamines; 0/Procollagen; 147-85-3/Proline; 2517-04-6/Azetidinecarboxylic Acid; 9007-34-5/Collagen

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


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