Stress induction of the spermidine/spermine N¹-acetyltransferase by a post-transcriptional mechanism in mammalian cells

Heat shock and diethyldithiocarbamate stimulate polyamine catabolism in animal cells by a mechanism involving the induction of spermidine/spermine N¹-acetyltransferase (N¹-SSAT) activity. Steady-state levels of RNA encoding this enzyme remain essentially unchanged during periods after these stresses when N¹-SSAT activity is increased by 3.5-10-fold or more in three different cell lines of hamster and human origin. Depletion of intracellular spermidine pools by α-difluoromethylornithine (DFMO) inhibits stress induction of N¹-SSAT activity. Exogenous spermidine can restore stress inducibility of N¹-SSAT to DFMO-treated cells, and induce this enzyme activity in non-heat-shocked but polyamine-depleted cells. Acetylation at N¹ suppresses the ability of spermidine to induce N¹-SSAT activity, relative to this same modification at N⁸. Fluorinated spermidine analogues, which decrease the pK(a) values of the amine groups at positions 4 and 8, neither induce nor inhibit N¹-SSAT activity in DFMO-treated cells. These data demonstrate that certain stresses induce N¹-SSAT by a spermidine-dependent post-transcriptional mechanism. The mode of induction is affected by both the propyl and butyl moieties of spermidine.