Regulation of ornithine decarboxylase by diamines in regenerating rat liver

Inhibition of ornithine decarboxylase by diamines in regenerating rat liver Evidence for direct action on the accumulation of the enzyme protein

“…It is thus unlikely that any protein inhibitors ('antizymes' [7,8] [6]. We have been able to partially confirm the induction of non-dialyzable inhibitors for ornithine decarboxylase in response to diamine administration in regenerating rat liver.…”

“…However, they were unable to detect similar inhibitors in normal or transformed Swiss 3T3 cells or cultured human fibroblasts after exposure of the cells to putrescine [9]. We have likewise been unable to obtain' any convincing evidence that the swift decay of ornithine decarboxylase in regenerating rat liver after injection of diamines would be based North-Holland Publishing Company -Amsterdam upon a formation of macromolecular inhibitors [6]. Extending this approach, we have further explored the mechanism of action of diamines on ornithine decarboxylase in regenerating rat liver.…”

“…The prevention of ornithine decarboxylase induction by putrescine and diaminopropane [2,6] in rat liver immediately after partial hepatectomy resembles the action achieved with inhibitors of RNA synthesis [6] whereas, during later periods of liver regeneration, the administration of the diamines results in an extremely swift decay of ornithine decarboxylase activity, suggesting a direct translational inhibition [2,5,6].…”

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.…”

Antiproliferative effects of inhibitors of polyamine synthesis in tumors of neural origin

“…Among these are competitive inhibitors such as a-methylornithine (22,25,26) and diamines such as 1,3-propanediamine, 1,5-pentanediamine, and l,6-hexanediamine. The diamines have been shown to act by inducing the formation of macromolecular inhibitors of ornithine decarboxylase (27,28) and by repressing the induction of the enzyme (28)(29)(30)(31)(32). The repression of enzyme synthesis has a relatively selective effect on ornithine decarboxylase; however, S-adenosylmethionine decarboxylase activity is inhibited slightly (33).…”