Regulation of ornithine decarboxylase in murine erythroleukemic cells by N,N'-diacetyl-1,6-hexanediamine and N-acetyl-1,6-hexanediamine.

Abstract

The levels at which the ornithine decarboxylase gene is regulated in murine erythroleukemic cells treated with N,N'-hexamethylene bisacetamide (N,N' diacetyl-1,6-hexanediamine) and with N-acetyl-1,6-hexanediamine, the monoacetylated catabolite of this inducer of erythrodifferentiation, have been investigated. Although these two molecules are structurally related and both cause a decrease in ornithine decarboxylase activity, they did not similarly affect ornithine decarboxylase mRNA. In the presence of 4 mM N,N'-hexamethylenebisacetamide, at the concentration generally used to induce differentiation in these cells, a decreased steady-state level of ornithine decarboxylase mRNA, due to decreased gene transcription, was observed. In the presence of N-acetyl-1,6-hexanediamine the decrease in enzyme activity was shown to be associated with a decrease in the half-life of the enzyme in the absence of a change in gene transcription. These results show that in proliferating cultured cells changes in ornithine-decarboxylase-gene transcription can be uncoupled from changes in cell growth and that N-acetyl-1,6-hexanediamine only regulates ornithine decarboxylase expression post-transcriptionally.