Polyamine regulation of ornithine decarboxylase and its antizyme in intestinal epithelial cells.
Ornithine decarboxylase (ODC) is feedback regulated by polyamines. ODC antizyme mediates this process by forming a complex with ODC and enhancing its degradation. It has been reported that polyamines induce ODC antizyme and inhibit ODC activity. Since exogenous polyamines can be converted to each other after they are taken up into cells, we used an inhibitor of S-adenosylmethionine decarboxylase, diethylglyoxal bis(guanylhydrazone) (DEGBG), to block the synthesis of spermidine and spermine from putrescine and investigated the specific roles of individual polyamines in the regulation of ODC in intestinal epithelial crypt (IEC-6) cells. We found that putrescine, spermidine, and spermine inhibited ODC activity stimulated by serum to 85, 46, and 0% of control, respectively, in the presence of DEGBG. ODC activity increased in DEGBG-treated cells, despite high intracellular putrescine levels. Although exogenous spermidine and spermine reduced ODC activity of DEGBG-treated cells close to control levels, spermine was more effective than spermidine. Exogenous putrescine was much less effective in inducing antizyme than spermidine or spermine. High putrescine levels in DEGBG-treated cells did not induce ODC antizyme when intracellular spermidine and spermine levels were low. The decay of ODC activity and reduction of ODC protein levels were not accompanied by induction of antizyme in the presence of DEGBG. Our results indicate that spermine is the most, and putrescine the least, effective polyamine in regulating ODC activity, and upregulation of antizyme is not required for the degradation of ODC protein.
Yuan
Q
Q
Department of Physiology, College of Medicine, The University of Tennessee, Memphis, Tennessee 38163, USA.
Ray
R M
RM
Viar
M J
MJ
Johnson
L R
LR
D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D005326:Fetal Proteins / Q000494:pharmacology; D007422:Intestines / Q000166:cytology* / Q000201:enzymology; D008935:Mitoguazone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011073:Polyamines / Q000493:pharmacokinetics*; D011700:Putrescine / Q000493:pharmacokinetics; D051381:Rats; D012436:S-Adenosylmethionine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013095:Spermidine / Q000493:pharmacokinetics; D013096:Spermine / Q000493:pharmacokinetics
D004791:Enzyme Inhibitors; D005326:Fetal Proteins; D011073:Polyamines; C056522:diethylglyoxal bis(guanylhydrazone); D013096:Spermine; D012436:S-Adenosylmethionine; D009955:Ornithine Decarboxylase; D008935:Mitoguazone; D013095:Spermidine; D011700:Putrescine