Polyamine regulation of ornithine decarboxylase and its antizyme in intestinal epithelial cells

Ornithine decarboxylase (ODC) is feedback regulated by polyamines. ODC anti zyme mediates this process by forming a complex with ODC and enhancing its degradation. It has been reported that polyamines induce ODC antizyme and i nhibit ODC activity. Since exogenous polyamines can be converted to each ot her after they are taken up into cells, we used an inhibitor of S-adenosylm ethionine decarboxylase, diethylglyoxal bis(guanylhydrazone) (DEGBG), to bl ock the synthesis of spermidine and spermine from putrescine and investigat ed the specific roles of individual polyamines in the regulation of ODC in intestinal epithelial crypt (IEC-6) cells. We found that putrescine, spermi dine, and spermine inhibited ODC activity stimulated by serum to 85, 46, an d 0% of control, respectively, in the presence of DEGBG. ODC activity incre ased in DEGBG-treated cells, despite high intracellular putrescine levels. Although exogenous spermidine and spermine reduced ODC activity of DEGBG-tr eated cells close to control levels, spermine was more effective than sperm idine. Exogenous putrescine was much less effective in inducing antizyme th an spermidine or spermine. High putrescine levels in DEGBG-treated cells di d not induce ODC antizyme when intracellular spermidine and spermine levels were low. The decay of ODC activity and reduction of ODC protein levels we re not accompanied by induction of antizyme in the presence of DEGBG. Our r esults indicate that spermine is the most, and putrescine the least, effect ive polyamine in regulating ODC activity, and upregulation of antizyme is n ot required for the degradation of ODC protein.