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Spermidine/spermine acetyltransferase

Cells treated with 5-FU undergo cell cycle arrest or apoptosis by inhibition of DNA synthesis. When human oral squamous cell carcinomas (HSC-2, HSC-3, HSC-4) were treated with 5-FU, viable cell numbers declined dose-dependently (CC50 determined after 24 hours treatment 3.4,6.9 and 1.7 p,M, respectively). The intracellular putrescine concentration slightly declined (Table 2) [29]. The combination treatment of 5-FU with N(l),N(ll)-diethylnorspermine (DEN-SPM), which is an inducer of spermidine/spermine N(l)-acetyltransferase (SSAT) that depletes polyamine, has been reported to augment the cytotoxic activity of 5-FU, suggesting possible clinical application [30]. [Pg.164]

Wang Y, Devereux W, Stewart TM, Casero RA Jr. 2001. Characterization of the interaction between the transcription factors human polyamine modulated factor (PMF-1) and NF-E2-related factor 2 (Nrf2) in the transcriptional regulation of the spermidine/spermine iV -acetyltransferase (SSAT) gene. Biochem. J. 355 45 9... [Pg.259]

The phosphinic acid polyamine analogue 370 is reported to be an effective inhibitor of purified human spermidine/spermine-N I-acetyltransferase (SSAT) and is claimed to be only the second example of a functional, non-superinducing inhibitor of human SSAT. The long-chain phosphonate analogues 371 and 372 are reported to exhibit cytostatic activity in vitro " ... [Pg.146]

Saab, N.H., West, E.E., Bieszk, N.C., Pteuss, C.V., Mank, A.R., Casero, R.A. Jr, and Woster, PJ. (1993) Synthesis and evaluation of unsymmetrically substituted polyamine analogues as modulators of human spermidine/spermine-lV -acetyltransferase (SSAT) and as potential antitumor agents. J. Med. Chem. 36 2998-3004. [Pg.271]

Keywords Aldehyde Epigenetic Inflammation Reactive oxygen species Spermidine/spermine A -acetyltransferase Spermine oxidase... [Pg.61]

In mammalian cells, the catabolism of spermine to spermidine occurs via one of two distinct pathways. As a substrate for spermidine/spermine IV -acetyltransferase (SSAT), spermine can be converted to A -acetylspermine, which is subsequently oxidized by the FAD-dependent acetylpolyamine oxidase (APAO) to form spermidine. Conversely, spermine can be directly oxidized by spermine oxidase (SMOX) to form spermidine. Spermidine is then back-converted to putrescine through the two-step SSAT/APAO reaction that includes an Af-acetylspermidine intermediate (Fig. 5.1). [Pg.62]

Fig. 5.1 The mammalian polyamine catabolic pathway. Spermine (Spm) is back-converted to spermidine (Spd) by either spermine oxidase SMOX) or spermidine/spermine Af-acetyltransferase SSAT) followed by acetylpolyamine oxidase APAO). Spermidine is further back-converted to putrescine Put) through the same SSAT/APAO mechanism. Both oxidation reactions generate the reactive oxygen species ROS) precursor H2O2 and aldehydes as by-products. The resulting reduction in spermine and spermidine pools implies diminished antioxidant and antiinflammatory functions... Fig. 5.1 The mammalian polyamine catabolic pathway. Spermine (Spm) is back-converted to spermidine (Spd) by either spermine oxidase SMOX) or spermidine/spermine Af-acetyltransferase SSAT) followed by acetylpolyamine oxidase APAO). Spermidine is further back-converted to putrescine Put) through the same SSAT/APAO mechanism. Both oxidation reactions generate the reactive oxygen species ROS) precursor H2O2 and aldehydes as by-products. The resulting reduction in spermine and spermidine pools implies diminished antioxidant and antiinflammatory functions...
Babbar N.GernerEW, Casero RA Jr (2006a) Induction of spermidine/spermine N1 -acetyltransferase (SSAT) by aspirin in Caco-2 colon cancer cells. Biochem J 394 317-324 Babbar N, Hacker A, Huang Y, Casero RA Jr (2006b) Tumor necrosis factor alpha induces spermidine/spermine N 1-acetyltransferase through nuclear factor kappaB in non-small cell lung cancer cells. J Biol Chem 281 24182-24192... [Pg.71]

Chopra S, Wallace HM (1998) Induction of spermidine/spermine Nl-acetyltransferase in human cancer cells in response to increased production of reactive oxygen species. Biochem Pharmacol 55 1119-1123... [Pg.72]

Fioii LM, Turecki G (2011) Epigenetic regulation of spermidine/spermine Nl-acetyltransferase (SATl) in suicide. J Psychiatr Res 45 1229-1235... [Pg.72]

Wang Y, Xiao L, ThiagaUngam A, NeUdn BD, Casero RA Jr (1998) The identification of a cis-element and a trans-acting factor involved in the response to polyamines and polyamine analogues in the regulation of the human spermidine/spermine Nl-acetyltransferase gene transcription. J Biol... [Pg.74]

Zahedi K, Soleimani M (2011) Spennidine/spermine-N(l)-acetyltransferase in kidney ischemia reperfusion injury. Methods Mol Biol 720 379-394 Zahedi K, Lentsch AB, OkayaT, Barone S, Sakai N, Witte DP, ArendLJ, Alhonen L, JeU J, Janne J, Porter CW, Soleimani M (2009) Spermidine/spermine-Nl-acetyltransferase ablation protects against liver and kidney ischemia-reperfiision injury in mice. Am J Physiol Gastrointest Liver Physiol 296 899-909... [Pg.74]

Zahedi K, Barone SL, Xu J, Steinbergs N, Schuster R, LentschAB, Amlal H, Wang J, Casero RA Jr, Soleimani M (2012) Hepatocyte-specific ablation of spermine/spermidine-Nl-acetyltransferase gene reduces the severity of CC14-induced acute liver injury. Am J Physiol Gastrointest Liver Physiol 303 546-560... [Pg.75]

Translational control of polyamine catabolism has been reported in mammals (Ivanov et al. 2010 Perez-Leal and Merali 2012). Spermidine/spermine V -acetyltransferase (SSAT) is the rate-Umiting enzyme for PA catabolism and is... [Pg.113]

Butcher NJ, Broadhurst GM, Mincfam RF (2007) Polyeimine-dependent regulation of spermidine-spermine fV-l-acetyltransferase mRNA translation. J Biol Chem 282 28530-28539 Calvo SE, Pagharini DJ, Mootha VK (2009) Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. Proc Natl Acad Sci USA 106 7507-7512... [Pg.116]

Parry L, Balana Fouce R, Pegg AE (1995) Post-transcriptional regulation of the content of spermidine/ spermine A -acetyltransferase by A A -bislethyllspermine. Biochem J 305 451 58 Peremarti A, Bassie L, Zhu C et al (2010) Molecular characterization of the Arginine decarboxylase gene family in rice. Transgenic Res 19 785-797... [Pg.118]

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Acetyltransferase

Spermidine

Spermidine acetyltransferase

Spermidine/spermine acetyltransferase SSAT)

Spermine

Spermine/spermidine

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