Regulation of spermidine/spermine N1-acetyltransferase by intracellular polyamine pools : Evidence for a functional role in polyamine homeostasis

• Published in: FEBS letters Vol. 321; no. 2; pp. 179 - 183
• Main Authors: Shappell, N.W., Fogel-Petrovic, M.F., Porter, C.W.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 26.04.1993; Elsevier
• Subjects: Acetyltransferases - genetics; Acetyltransferases - metabolism; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Blotting, Northern; Eflornithine - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic - drug effects; Homeostasis; Humans; Melanoma; Models, Biological; Non peptidic neurotransmitters, polyamines; Other biological molecules; Polyamine; Polyamine homeostasis; Polyamines - metabolism; Polyamines - pharmacology; Putrescine - metabolism; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Spermidine; Spermidine - metabolism; Spermidine - pharmacology; Spermidine/spermine N1-acetyltransferase; Spermine; Spermine - metabolism; Spermine - pharmacology; Tumor Cells, Cultured; Polyamine; Polyamine homeostasis; AMA, S-(5'-deoxy-5-adenosyl)-methylthioethylhydroxylamine; SPM, spermine; ODC, ornithine decarboxylase; SSAT, spermidine/ spermine- N 1-acetyltransferase; Spermine; Spermidine/spermine N 1-acetyltransferase; PUT, putrescine; Spermidine; DFMO, α-difluoromethylornithine; SPD, spermidine; SAMDC, S-adenosylmethionine decarboxylase; Human; Cell line; Enzyme; Melanoma; Homeostasis; Feedback regulation; Spermidine N-acetyltransferase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(93)80103-2

Through its role in polyamine acetylation and the back-conversion pathway, spermidine/spermine N 1-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 MALME-3 human melanoma cells. Increases in intracellular polyamine pools by treatment with 3 μM exogenous spermidine or spermine for 48 h caused SSAT activity to increase 111% and 226%, respectively, and SSAT-specific mRNA to rise 19% and 66%, 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.