Ornithine decarboxylase and polyamines in liver and kidneys of rats on cyclical regimen of protein-free and protein-containing diets. Relationship to deoxyribonucleic acid synthesis in liver

Abstract

1. The activity of ornithine decarboxylase in the liver and kidneys of rats maintained on a cyclical regimen of protein-free and protein-containing diets was investigated. There was a daily activation of the enzyme in response to the feeding of protein after 3 days feeding of protein-free diet. 2. The activation of ornithine decarboxylase in the liver and kidneys of rats re-fed on protein was demonstrable throughout 16 cycles of alternating 3-day periods of protein-free and protein-containing diets. The magnitude of the activation in the kidneys diminished from 20-fold stimulation in the first cycle to 5-fold stimulation (compared with animals fed with protein-free diet) in the later cycles of protein re-feeding. The activation of the enzyme in liver was decreased from 20-fold stimulation in the first cycle to approx. 10-fold stimulation in later cycles. 3. The concentration of spermidine was increased by approx. 50% in the liver of animals during cycling from protein-free to protein-containing diets. Spermine was unchanged, and putrescine was maintained at a low concentration approx. one-fifth to one-tenth that of spermidine after protein re-feeding. 4. The incorporation of [(3)H]thymidine into liver DNA was increased 10-fold in animals re-fed with protein compared with animals receiving protein-free diets. 5. The activation of ornithine decarboxylase by re-feeding of protein was inhibited 90% by the injection of propane-1,3-diamine during re-feeding. The stimulation of DNA synthesis was inhibited 60% by multiple injections of propane-1,3-diamine during the re-feeding of protein.

Role of Polyamines in the Control of Cell Proliferation and Differentiation

“…They are repression-type inhibitors of ODC (the ODC activity of a crude enzyme preparation is not blocked by this category of inhibitors) and inhibit competitively (with respect to the polyamine substrate) the spermidine and spermine synthase reactions (Table 1). Treatment with 1,Idiaminopropane effectively represses the induction of ODC activity and blocks the accumulation of putrescine and spermidine that occur in the rat liver stimulated to proliferate by partial hepatectomy [53, 92,107,1081 or by refeeding after starvation [109,1101. The suppression of polyamine synthesis caused by 1.3-diaminopropane treatment was accompanied by a marked inhibition of DNA synthesis [53, 92, 107-1091 and, as a consequence, subsequent mitotic activity [110].…”

Reversible inhibition of rat liver regeneration by 1,3‐diamino‐2‐propanol, an inhibitor of ornithine decarboxylase

“…Indirect amine inhibitors of omithine decarboxylase (such as 1,3-diaminopropane), which may act through an induction of protein inhibitors to the enzyme [30] or through more direct transcriptional or translational control mechanisms [31 ], have likewise been employed to abolish polyamine accumulation in regenerating rat liver [7][8][9], in rat liver during refeeding [32] and ovary cells grown in culture [33]. In every instance, the prevention of enhanced spermidine and/or putrescine accumulation was associated with distinct decreases in the synthesis of DNA.…”

Effects of acute and chronic protein deprivation on ornithine decarboxylase levels in rat liver and colon

“…Previously, studies showed that a decrease in hepatic and colonic ODC activity occurred in rats after 48 hours of starvation [25]. Shortterm feeding (1-3 days) of a protein-free diet also depressed hepatic ODC activity [26]. The chronic or long-term effects of feeding low dietary protein on rat hepatic ODC activity have not been closely examined nor has the response of colonic ODC activity to low-protein diet.…”