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Structure-function correlations of polyamine analog-induced increases in spermidine/spermine acetyltransferase
P R Libby1, R J Bergeron, C W Porter
1Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, NY 14263.
Biochemical Pharmacology
|May 1, 1989
Summary
Spermidine/spermine acetyltransferase (SSAT) activity is significantly induced by polyamine analogs N1,N8-bis(ethyl)spermidine (BES) and N1,N12-bis(ethyl)spermine (BESm). This induction involves increased protein synthesis and enzyme stabilization, independent of other cellular effects.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- Spermidine/spermine acetyltransferase (SSAT) is a key enzyme in polyamine metabolism.
- SSAT exhibits high inducibility in response to various stimuli.
- Polyamines play crucial roles in cell growth and proliferation.
Purpose of the Study:
- To identify potent inducers of SSAT activity among polyamine analogs.
- To elucidate the mechanisms underlying SSAT induction.
- To investigate structure-function relationships of polyamine analogs in SSAT induction.
Main Methods:
- Cultured L1210 cells were treated with various polyamines and analogs.
- SSAT activity was measured over time.
- Inhibitor studies were conducted to determine mechanisms of induction.
- Structure-activity relationships were analyzed.
Main Results:
- N1,N8-bis(ethyl)spermidine (BES) and N1,N12-bis(ethyl)spermine (BESm) were identified as potent SSAT inducers.
- BESm treatment led to a 16-fold increase in SSAT activity within 24 hours, reaching 20-fold by 48 hours.
- Induction was attributed to increased protein synthesis (translation) and prolonged enzyme half-life.
- Optimal induction required specific aminopropyl moieties and alkyl group characteristics.
Conclusions:
- BES and BESm are highly effective inducers of SSAT activity in L1210 cells.
- The induction mechanism involves both transcriptional and post-translational regulation.
- The effects of BES and BESm on SSAT activity are distinct from their roles in regulating other enzymes or inhibiting cell growth.