Metabolism of N-alkylated spermine analogues by polyamine and spermine oxidases

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Consequences of Spermine Synthase or Spermidine/Spermine N- Acetyltransferase Deficiency in Polyamine Metabolism

A vast number of studies have linked polyamines to numerous cellular functions but less is known about the possible physiological functions of the individual polyamines. The specific gene targeting technique has provided a new potential way to resolve this mystery. We generated two separate embryonic stem (ES) cell lines where either spermine synthase gene (SPMSy) or spermidine/spermine N-acety...

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Inhibition of acetylpolyamine and spermine oxidases by the polyamine analogue chlorhexidine.

Acetylpolyamine and spermine oxidases are involved in the catabolism of polyamines. The discovery of selective inhibitors of these enzymes represents an important tool for the development of novel anti-neoplastic drugs. Here, a comparative study on acetylpolyamine and spermine oxidases inhibition by the polyamine analogue chlorhexidine is reported. Chlorhexidine is an antiseptic diamide, common...

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N1-dansyl-spermine: a potent polyamine antagonist.

The potential polyamine antagonist action of N1-dansyl-spermine (a potent NMDA antagonist) was assessed in two in vivo mouse models of polyamine action. Co-administration of N1-dansyl-spermine (2-10 microg, i.c.v.) with spermine (100 microg, i.c.v.) resulted in a dose-dependent antagonism of the spermine-induced CNS excitation (body tremor and fatal tonic convulsions). In addition, the same dos...

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Major increases in spermidine/spermine-N1-acetyltransferase activity by spermine analogues and their relationship to polyamine depletion and growth inhibition in L1210 cells.

As an antiproliferative strategy, we are using bis(ethyl) derivatives of spermine to suppress polyamine biosynthetic enzyme activity and, thereby, deplete intracellular polyamine pools. Since certain of these analogues have recently been shown to potently increase spermidine/spermine-N1-acetyltransferase activity, we have investigated the relationship of this effect to growth inhibition and pol...

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Polyamine-dependent regulation of spermidine-spermine N1-acetyltransferase mRNA translation.

Spermidine-spermine N(1)-acetyltransferase (SSAT) is induced in response to an elevation in intracellular polyamine pools. The increased enzyme activity is the result of an increase in gene transcription, mRNA translation, and protein stability. Induction of SSAT by polyamine analogues can lead to intracellular polyamine depletion and apoptosis. The mechanism by which polyamines alter the trans...

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ژورنال

عنوان ژورنال: Amino Acids

سال: 2009

ISSN: 0939-4451,1438-2199

DOI: 10.1007/s00726-009-0429-2