Regulation of spermidine/spermine N¹‐acetyltransferase by intracellular polyamine pools

Abstract

Through its role in polyamine acetylation and the back-conversion pathway, spermidine&ermine N'-acetyltransferase (SSAT) has the potential to control intracellular polyamine pools by facilitating their catabolism and/or excretion. The possibility that the enzyme is subject to regulation by intracellular polyamine pools was investigated in MALME3 human melanoma cells. Increases in intracellular polyamine pools by treatment with 3 PM exogenous spermidine or spermine for 48 h caused SSAT activity to increase 111% and 22696, respectively, and SSAT-specific mRNA to rise 19% and 6646, respectively. Decreases in polyamine pools by treatment with inhibitors of polyamine biosynthesis caused SSAT activity to decrease by 46% and mRNA to fall by 89%. Both SSAT activity and mRNA were more sensitive to changes in spermine than spermidine. The identification of a positive regulatory relationship between SSAT and intracellular polyamine pools further implicates this enzyme in a proposed model for polyamine pool homeostasis.

Differential post‐transcriptional control of ornithine decarboxylase and spermidine‐spermine N1‐acetyltransferase by polyamines

“…Since this is far less than expected on the basis of available CHX-induced mRNA (i.e. 9-fold at the beginning of the post-incubation, 6-fold at the end) and since SSAT is known to be positively regulated by polyamines [4,12], the possibility was considered that mRNA translation may be restricted by Northern blot of SSAT mRNA (left) and bar graph of SSAT activity (right) from MALME-3M cells treated for 6 h in the presence or absence of CHX (at 10 lag/ml), washed and then post-incubated for an additional 6 h in the presence or absence SPM or SPD. Incubations with SPM were also carried out with the transcription inhibitor dichlorobenzimidazole (DRB, at 25 lag/ml).…”

Disrupted Spermine Homeostasis: A Novel Mechanism in Polyglutamine-Mediated Aggregation and Cell Death

“…SSAT mRNA and protein expression are tightly regulated by intracellular polyamine levels and are part of a feedback system controlling cytosolic spermine concentrations (Porter et al, 1990). Thus, SSAT mRNA increases with increased cytosolic spermine concentration (Shappell et al, 1993;Fogel-Petrovic et al, 1996;Shantz and Pegg, 1999;Suppola et al, 2001). No significant differences were observed in the basal level of SSAT mRNA between polyQ19-YFP and polyQ57-YFP CAD cells.…”

“…To determine whether polyamine metabolism is altered in polyQ57 cells, we next examined SSAT, the enzyme that catalyzes the back-conversion of spermine to N-acetylspermine (Pohjanpelto et al, 1985;Shappell et al, 1993;Suppola et al, 2001;Wallace et al, 2003). SSAT mRNA and protein expression are tightly regulated by intracellular polyamine levels and are part of a feedback system controlling cytosolic spermine concentrations (Porter et al, 1990).…”

“…SSAT, the enzyme that catalyzes the back-conversion of spermine to N-acetyl forms, is tightly regulated by intracellular spermine. Under normal physiological conditions, increased cytosolic spermine induces a rapid, transient rise in SSAT mRNA and protein (Shappell et al, 1993;Fogel-Petrovic et al, 1996;Shantz and Pegg, 1999;Suppola et al, 1999). As a consequence, spermine levels are lowered by the back-conversion of spermine to N-acetylspermine that is either transported out of the cells or recycled to lower polyamines.…”

“…As a consequence, spermine levels are lowered by the back-conversion of spermine to N-acetylspermine that is either transported out of the cells or recycled to lower polyamines. This tight feedback regulation of SSAT mRNA by intracellular spermine levels can be used to indicate cellular spermine production (Shappell et al, 1993;Pietila et al, 1997). CAD cells expressing polyQ19-YFP have a functional feedback control system because activation of polyamine production by 8-Br-cAMP plus L-vNIO resulted in increased and then decreased SSAT mRNA as predicted from its role in the homeostatic control of free spermine levels inside the cell.…”