Aging and polyamine acetylation in rat kidney

Abstract

The acetylation of polyamines was investigated in rat kidney as a function of age. The activity of cytosolic spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in polyamine interconversion, increased from 3 to 36 months of age. The activity of cytosolic spermidine N8-acetyltransferase, an enzyme probably related to polyamine excretion, also increased. The activity of polyamine oxidase, which catalyzes the oxidative cleavage of polyamine N1-acetyl derivatives into putrescine, decreased until 24 months, when an accumulation of N1-acetylspermidine occurred. Subsequently, at 36 months, polyamine oxidase activity returned toward high values, in concomitance with the disappearance of N1-acetylspermidine, an increase in spermidine and putrescine, and a decline in spermine was observed. Our results show that in rat kidney during aging there is an activation of the acetylation and interconversion of higher polyamines into putrescine, which is considered an alternative pathway of spermidine and putrescine formation.

Gender-related differences in polyamine oxidase activity in rat tissues

“…In our thymic and hepatic extracts, spermidine was prevalently acetylated; histones (the preferred substrate of nuclear N s-SAT (Libby, 1978;Wallace et al, 1992)) were also acetylated to a high degree, whereas putrescine (another substrate for nuclear enzyme (Wallace et al, 1992)) was only slightly acetylated in male and in female rats. These results indicate that two enzymes acetylating spermidine in the N 1 and the N s position, respectively, were present in our cytosolic extracts, as previously reported (Wallace et al, 1992;Ferioli et al, 1996). The activity levels of PAO in several tissues of young rats is shown in Fig.…”

“…The present results confirm the data of Tanaka et al (1993) on the sex-related difference in hepatic SAT activity and extend the knowledge by reporting the same gender-related difference in the activity of the second catabolic enzyme, PAO. This enzyme has been scarcely investigated, in contrast to the key enzymes of polyamine biosynthesis and SAT, and the availability of pure PAO from tissues other than the liver (H61tt~i, 1977) would be of great interest in understanding the role of the enzyme in polyamine metabolism, since changes in PAO activity in different experimental conditions have been shown (Hayashi et al, 1989;Sessa et al, 1995;Dimitrov et al, 1996;Ferioli et al, 1996). No reasons for the genderrelated differences in PAO activity can be given on the basis of the present study.…”

“…However, there is another step of polyamine metabolism that involves oxidative deacetylation of monoacetyl derivatives of polyamines by the action of the flavin-containing polyamine oxidase (EC 1.5.3.3,PAO), the importance of which has only been recently assessed. However, changes in PAO activity have been demonstrated in tissues during postnatal development or ageing and after treatment with certain drugs, hormones or hyperplastic factors (Hayashi et al, 1989;Sessa et al, 1995;Dimitrov et al, 1996;Ferioli et al, 1996). All these data suggest an important role also for PAO in the regulation of intracellular levels of polyamines, as previously postulated (H61ttfi, 1977;Morgan, 1981).…”

Histone deacetylase-10 liberates spermidine to support polyamine homeostasis and tumor cell growth

“…N 8 -AcSpd has also been shown to increase with age in the rat kidney, alongside an increase in spermidine acetyltransferase activities ( 36 ). As de novo polyamine biosynthesis decreases with age in many tissues ( 37 ), it has been suggested that maintaining acetylated spermidine pools, including N 8 -AcSpd, might compensate by increasing polyamine interconversion ( 36 ). In fact, HDAC10 is highly expressed in the kidney, as well as the spleen and liver ( 38 ).…”

Assay of N1-Acetylpolyamine Oxidase Activity with N1,N11-Didansylnorspermine as the Substrate by Ion-Pair Reversed Phase High Performance Liquid Chromatography

“…1) Until several years ago, PAO was believed to be a constitutive enzyme with little is known about its physiological relevance. However, changes in PAO activity have been demonstrated in tissues during postnatal development or aging [4][5][6] and after treatment with certain drugs [7][8][9] or hormones, [10][11][12][13] confirming the inducibility of the enzyme. Recently, another polyamine catabolic enzyme was cloned as spermine oxidase (SMO) which oxidizes spermine (Spm) to Spd with H 2 O 2 production and is inducible when cells are treated with anticancer drugs.…”