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

Abstract

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 alpha-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 pKa 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.

Cryptosporidium parvum Induces an Endoplasmic Stress Response in the Intestinal Adenocarcinoma HCT-8 Cell Line

“…Blockade of spermidine synthesis by inhibition of ODC results in elevation of the retroconversion pathway, in particular SSAT-1, which provides a source of spermidine (29,30); the lack of parasite ODC and acquisition of host cell N-acetylspermine explain in part these earlier observations with DL-␣-difluoromethylornithine. The dependence of C. parvum upon host cell polyamine biosynthesis may be an important avenue to control infection by C. parvum via modulating host cell polyamine biosynthesis.…”

Effect of Nicotine on Lung S-Adenosylmethionine and Development of Pneumocystis Pneumonia

“…Because shifts in polyamine metabolism in response to stress are known, particularly increases in SSAT activity (47,59), and nicotine treatment requires weeks to have full effect on lung AdoMet, the effect of nicotine on lung AdoMet may be part of a multistep stress response that culminates in changed polyamine metabolism. However, a previous study reported a 25-fold increase in lung ODC activity in animals 4 h after a dose of 5 mg nicotine kg Ϫ1 (57) so that it is also possible the primary effect is on polyamine pathways with AdoMet depletion being due to the cumulative effect of greater AdoMet consumption than production over weeks.…”

Elevated N1‐Acetylspermidine Levels in Gerbil and Rat Brains After CNS Injury

“…This suggests that the induction of SSAT (Zoli et al, 1996) and PAO (Baudry and Najm, 1994;Hayashi and Baudry, 1995;Ivanova et al, 1998), which convert spermine and spermidine to putrescine, probably is a major pathway accounting for putrescine accumulation at 1 day. These studies did not attempt to correlate SSAT enzymatic activity to N 1 -acetylspermidine levels because the SSAT assay may overestimate N 1 -SSAT activity (Persson and Pegg, 1984;Gerner et al, 1993).…”