Document Detail


Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels.
MedLine Citation:
PMID:  9624108     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Polyamines are required for entry and progression of the cell cycle. As such, augmentation of polyamine levels is essential for cellular transformation. Polyamines are autoregulated through induction of antizyme, which represses both the rate-limiting polyamine biosynthetic enzyme ornithine decarboxylase and cellular polyamine transport. In the present study we demonstrate that agmatine, a metabolite of arginine via arginine decarboxylase (an arginine pathway distinct from that of the classical polyamines), also serves the dual regulatory functions of suppressing polyamine biosynthesis and cellular polyamine uptake through induction of antizyme. The capacity of agmatine to induce antizyme is demonstrated by: (a) an agmatine-dependent translational frameshift of antizyme mRNA to produce a full-length protein and (b) suppression of agmatine-dependent inhibitory activity by either anti-antizyme IgG or antizyme inhibitor. Furthermore, agmatine administration depletes intracellular polyamine levels to suppress cellular proliferation in a transformed cell line. This suppression is reversible with polyamine supplementation. We propose a novel regulatory pathway in which agmatine acts as an antiproliferative molecule and potential tumor suppressor by restricting the cellular polyamine supply required to support growth.
Authors:
J Satriano; S Matsufuji; Y Murakami; M J Lortie; D Schwartz; C J Kelly; S Hayashi; R C Blantz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  273     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-07-09     Completed Date:  1998-07-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  15313-6     Citation Subset:  IM    
Affiliation:
Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego and Veterans Affairs Medical Center, La Jolla, California 92161, USA. jsatriano@ucsd.edu
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Agmatine / pharmacology*
Animals
Biological Transport / drug effects
Carboxy-Lyases / metabolism*
Cell Division / drug effects*
Chromatography, High Pressure Liquid
Frameshifting, Ribosomal
Humans
Mice
Ornithine Decarboxylase / antagonists & inhibitors*
Polyamines / metabolism*
Protein Biosynthesis
Proteins / genetics*
Putrescine / pharmacology
Rats
Grant Support
ID/Acronym/Agency:
DK28602/DK/NIDDK NIH HHS; DK42155/DK/NIDDK NIH HHS; HL48108/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Polyamines; 0/Proteins; 0/ornithine decarboxylase antizyme; 110-60-1/Putrescine; 306-60-5/Agmatine; EC 4.1.1.-/Carboxy-Lyases; EC 4.1.1.17/Ornithine Decarboxylase; EC 4.1.1.19/arginine decarboxylase

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


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