Document Detail

Polyamine transport is mediated by both endocytic and solute carrier transport mechanisms in the gastrointestinal tract.
MedLine Citation:
PMID:  20522643     Owner:  NLM     Status:  MEDLINE    
The polyamines spermidine and spermine, and their precursor putrescine, are required for cell growth and cellular functions. The high levels of tissue polyamines are implicated in carcinogenesis. The major sources of exogenous polyamines are diet and intestinal luminal bacteria in gastrointestinal (GI) tissues. Both endocytic and solute carrier-dependent mechanisms have been described for polyamine uptake. Knocking down of caveolin-1 protein increased polyamine uptake in colon cancer-derived HCT116 cells. Dietary supplied putrescine was accumulated in GI tissues and liver in caveolin-1 knockout mice more than wild-type mice. Knocking out of nitric oxide synthase (NOS2), which has been implicated in the release of exogenous polyamines from internalized vesicles, abolished the accumulation of dietary putrescine in GI tissues. Under conditions of reduced endogenous tissue putrescine contents, caused by treatment with the polyamine synthesis inhibitor difluoromethylornithine (DFMO), small intestinal and colonic mucosal polyamine contents increased with dietary putrescine levels, even in mice lacking NOS2. Knocking down the solute carrier transporter SLC3A2 in HCT116-derived Hkh2 cells reduced the accumulation of exogenous putrescine and total polyamine contents in DFMO treated cells, relative to non-DFMO-treated cells. These data demonstrate that exogenous putrescine is transported into GI tissues by caveolin-1- and NOS2-dependent mechanisms, but that the solute carrier transporter SLC3A2 can function bidirectionally to import putrescine under conditions of low tissue polyamines.
Takeshi Uemura; David E Stringer; Karen A Blohm-Mangone; Eugene W Gerner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-06-03
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  299     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-29     Completed Date:  2010-08-30     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G517-22     Citation Subset:  IM    
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MeSH Terms
Antigens, CD98 Heavy Chain / metabolism*
Biological Transport / physiology
Caveolae / physiology
Caveolin 1 / deficiency,  metabolism*
Cell Line, Tumor
Colonic Neoplasms / metabolism,  pathology
Drug Combinations
Eflornithine / pharmacology
Endocytosis / physiology*
Enzyme Inhibitors / pharmacology
Gastrointestinal Tract / metabolism*
Mice, Knockout
Nitric Oxide Synthase / deficiency,  metabolism*
Putrescine / pharmacokinetics*
Spermidine / metabolism
Grant Support
Reg. No./Substance:
0/Antigens, CD98 Heavy Chain; 0/Caveolin 1; 0/Drug Combinations; 0/Enzyme Inhibitors; 0/Slc3A2 protein, mouse; EC Oxide Synthase; U87FK77H25/Spermidine; V10TVZ52E4/Putrescine; ZQN1G5V6SR/Eflornithine

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