Disease relevance of an N-acetylspermidine

• The association of N1-acetylspermidine with human colorectal adenocarcinomas has been evaluated in this study [1].
• At 18.3 nmol/mg creatinine, N1-acetylspermidine was 100% sensitive and specific for colon cancer [2].
• The N1-acetylspermidine levels in control mucosae on the oral and anal side of adenocarcinomas were 5.84 +/- 1.44 (n = 57) and 7.92 +/- 2.89 (n = 50) nmol/g, respectively; no significant difference was observed between control mucosae and adenomas [1].
• Treatment of the animals with N1,N2-bis-(2,3-butadienyl)-1,4-butanediamine (MDL 72527), a specific inhibitor of polyamine oxidase, caused large accumulation of N1-acetylspermidine in hepatoma cells and in the ascitic fluid; the maximal values were reached at day 14 [3].
• These data taken together with the analysis of urinary acetylpolyamines in rats bearing mammary tumors and in two melanoma patients show that the determination of the N1-acetylspermidine/N8-acetylspermidine ratio in urine may be of only limited value as an indicator for the presence of tumors [4].

High impact information on an N-acetylspermidine

• The urinary levels (expressed as nmol/mg creatinine) of putrescine, spermidine, spermine, N1-acetylspermidine, and N8-acetylspermidine were then analyzed by high-performance liquid chromatography [2].
• Urinary excretion of N1-acetylspermidine and other acetylated and free polyamines in the 1,2-dimethylhydrazine model of experimental rat colon cancer [2].
• 1,2-Dimethylhydrazine-induced alterations in N1-acetylspermidine levels and spermidine N1-acetyltransferase activity in rat colonic mucosa [5].
• N1-Acetylspermine was detected only when N1-acetylspermidine levels were very high after treatment with radical-producing drugs and lipopolysaccharide [6].
• These results suggest that the metabolism of N1-acetylspermidine in colorectal adenocarcinomas is quite different from that in adenomas and in nonneoplastic mucosae and that N1-acetylspermidine can be a promising biochemical marker of cancer in the human large intestine [1].

Chemical compound and disease context of an N-acetylspermidine

• These results suggest that the production of N1-acetylspermidine in human liver is closely associated with the induction of spermidine/spermine N1-acetyltransferase activity in liver diseases [7].
• Elevation of N1-acetylspermidine and putrescine in hepatic tissues of patients with fulminant hepatitis and liver cirrhosis [7].
• Isoprenaline treatment causes cardiac hypertrophy and an accumulation of N1-acetylspermidine in the rat heart [8].
• Since prior studies have indicated that diets high in fat, particularly unsaturated fat, promote the development of dimethylhydrazine-induced tumors, it was of interest to examine the effect of a corn oil dietary regimen (20% by weight) on colonic N1-acetylspermidine levels in this model of colonic adenocarcinoma [9].

Biological context of an N-acetylspermidine

• Thus, the spermidine transport system is strongly enhanced by hyposmotic shock in D-R cells, which can result in extensive cell death from overaccumulation of the polyamine and, to a lesser extent, from stress related to the PAO-catalyzed degradation of N1-acetylspermidine [10].
• Analysis of the polyamine substrate specificity for hypusine formation showed that N1-acetylspermidine did not compete with spermidine in the reaction, nor did N1-(buta-2,3-dienyl)-N2-methylbutane-1,4-diamine, and irreversible inhibitor of polyamine oxidase, block the reaction [11].
• N-(3-acetamidopropyl)pyrrolidin-2-one is formed from N1-acetylspermidine, since hydrolysis of tissue extracts of N1-acetylspermidine-treated mice produced isoputreanine [12].
• Other exogenously added polyamines including N1-acetylspermidine, spermidine, putrescine, and spermine did not stimulate cell growth [13].
• In contrast, MDL 72527 did not change the apoptosis rate and the N1-acetylspermidine content in cells treated with 7beta-OHsitosterol [14].

Anatomical context of an N-acetylspermidine

• Our data confirm that the hippocampus and cerebellum are glucocorticoid target tissues and suggest that the increase in the content of putrescine, following acute treatment with glucocorticoids, is dependent on ornithine decarboxylase as well as N1-acetylspermidine transferase induction [15].
• Occurrence in high concentrations of N1-acetylspermidine and syn-homospermidine in the hamster epididymis [16].
• Secretin-induced accumulation of N1-acetylspermidine and putrescine in the rat pancreas [17].
• The presence of N1-acetylspermidine already at the 8th day indicates that in chick embryo retina, putrescine synthesis can depend on two separate pathways [18].
• Moreover, the presence of N1-acetylspermidine already at the 7th day indicates that in the outer segment of photoreceptor cells too, as in the whole retina, putrescine synthesis comes about by two pathways [19].

Associations of an N-acetylspermidine with other chemical compounds

• This is reflected by a circadian rhythmicity undescribed previously in urinary monoacetylputrescine and the ratio of N1-acetylspermidine to N8-acetylspermidine in healthy individuals [20].
• SSAT products N(1)-acetylspermidine, N(1)-acetylspermine, and N(1),N(12)-diacetylspermine accumulated intracellularly and extracellularly [21].
• The great increases in ornithine decarboxylase and N1-acetylspermidine transferase activities were accompanied by a marked increase in putrescine level and a small decrease in spermidine level [15].
• The effect of glucocorticoids on polyamine metabolism has been elucidated further by measuring putrescine, spermidine, and spermine levels as well as ornithine decarboxylase, S-adenosylmethionine decarboxylase, and N1-acetylspermidine transferase activities in the hippocampus, cerebellar cortex, vermis, and deep nuclei of adrenalectomized rats [15].
• N1-Acetylspermidine (N1AcSpd) accumulates in late exponential phase, or after certain stresses such as heat shock, in both human tumour (A549) and rodent (HTC, CHO) cells, grown in medium containing an inhibitor of the FAD-dependent polyamine oxidase (PAO) [22].

Gene context of an N-acetylspermidine

• Here we report that PAO, which normally metabolizes achiral substrates, oxidized (R)-isomer of 1-amino-8-acetamido-5-azanonane and N1-acetylspermidine as efficiently while (S)-1-amino-8-acetamido-5-azanonane was a much less preferred substrate [23].
• In mammalian cells, the flavoprotein polyamine oxidase catalyzes a key step in the catabolism of polyamines, the oxidation of N1-acetylspermine and N1-acetylspermidine to spermidine and putrescine, respectively [24].
• The P. carinii SSAT K(m) value of 25 microM spermidine is 20% of that of mammalian cells, and the PAO K(m) value of 14 nM N(1)-acetylspermidine is 0.01% of that of mammalian cells [25].
• Tumor samples from transgenic animals showed marked elevations in SSAT enzyme activity and SSAT protein levels compared with tumors from non-transgenic littermates, and the accompanying changes in putrescine and N1-acetylspermidine pools indicated activation of SSAT-mediated polyamine catabolism in transgenic animals [26].
• Glucocorticoids suppress and oestrogens enhance the lipopolysaccharide-induced increase in putrescine and N1-acetylspermidine in mouse liver [27].

Analytical, diagnostic and therapeutic context of an N-acetylspermidine

• To determine whether the cardiac hypertrophy is the cause of the increase in N1-acetylspermidine, we produced cardiac hypertrophy by constriction of the aorta and analyzed polyamines in the hearts of these rats 1, 3, and 10 days after the aortic constriction [8].
• The antibody binding was inhibited most effectively by absorption of the antiserum with N1-acetylspermidine and Spd in the ELISA inhibition test [28].
• A single subcutaneous injection of monocrotaline produced dose- and time-dependent increases in the lung content of N1-acetylspermidine [29].
• Using gas chromatography mass spectrometry following derivatization (N-trifluoroacetylation), 1-N-acetylspermidine was found to occur in normal human serum at a level of approximately 0.008--0.5 nmol ml(-1), i.e. about two orders of magnitude lower than the corresponding spermidine level [30].

References