Polyamine transport is mediated by both endocytic and solute carrier transport mechanisms in the gastrointestinal tract.
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.
The Arizona Cancer Center, University of Arizona, Tucson, USA.
Takeshi
T
Uemura
David E
DE
Stringer
Karen A
KA
Blohm-Mangone
Eugene W
EW
Gerner
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002384:Catalysis; D021941:Caveolae / Q000502:physiology; D051242:Caveolin 1 / Q000172:deficiency / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D004338:Drug Combinations; D000518:Eflornithine / Q000494:pharmacology; D004705:Endocytosis / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000378:metabolism*; D011700:Putrescine / Q000493:pharmacokinetics*; D013095:Spermidine / Q000378:metabolism
D051242:Caveolin 1; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D027282:Fusion Regulatory Protein 1, Heavy Chain; C523212:Slc3A2 protein, mouse; D019001:Nitric Oxide Synthase; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine