Inhibition of Putrescine Aminopropyltransferase Influences Rat Liver Regeneration

Kobayashi, Masaki; Takao, Koichi; Shiota, Yasuo; Sugita, Yoshiaki; Takahashi, Masakazu; Nakae, Dai; Samejima, Keijiro

doi:10.1248/bpb.29.863

Cited by 6 publications

(5 citation statements)

References 21 publications

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“…As to polyamine metabolism, ROS and nitrogen species inactivate methionine adenosyltransferase I/III [33], reducing hepatic S-adenosylmethionine levels, which can regulate liver regeneration by forming spermidine and spermine [34, 35]. Furthermore, in colon carcinoma cells (HT-29 cells), the altered ornithine (ODC substrate) flux through urea cycle can lead to ammonia accumulation, reducing ODC activity which results in a decreased polyamine synthesis [36], indicating that the metabolic fate of ornithine is also involved in the polyamine synthesis.…”

Section: Discussionmentioning

confidence: 99%

Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

2016

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BackgroundThe pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH), by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of STAT-1 and -3 proteins and altering retinoid metabolism. Interactions between retinoic acid and polyamines have been reported in the PH-induced rat liver regeneration. Therefore, we evaluated the effect of low dosage of α-tocopherol on PH-induced changes in polyamine metabolism.MethodsThis study evaluated the participation of polyamine synthesis and metabolism during α-tocopherol-induced inhibition of rat liver regeneration. In PH-rats (Wistar) treated with α-tocopherol and putrescine, parameters indicative of cell proliferation, lipid peroxidation, ornithine decarboxylase expression (ODC), and polyamine levels, were determined.ResultsPre-treatment with α-tocopherol to PH-animals exerted an antioxidant effect, shifting earlier the increased ODC activity and expression, temporally affecting polyamine synthesis and ornithine metabolism. Whereas administration of putrescine induced minor changes in PH-rats, the concomitant treatment actually counteracted most of adverse actions exerted by α-tocopherol on the remnant liver, restituting its proliferative potential, without changing its antioxidant effect. Putrescine administration to these rats was also associated with lower ODC expression and activity in the proliferating liver, but the temporally shifting in the amount of liver polyamines induced by α-tocopherol, was also “synchronized” by the putrescine administration. The latter is supported by the fact that a close relationship was observed between fluctuations of polyamines and retinoids.ConclusionsPutrescine counteracted most adverse actions exerted by α-tocopherol on rat liver regeneration, restoring liver proliferative potential and restituting the decreased retinoid levels induced by α-tocopherol. Therefore interactions between polyamines and retinol, mediated by the oxidant status, should be taken into consideration in the development of new therapeutic strategies for pathologies occurring with liver cell proliferation.

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Section: Discussionmentioning

confidence: 99%

Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

2016

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“…15 N-Labeled polyamines, [1,[4][5][6][7][8][9][10][11][12][13][14][15] N 2 ]putrescine ( 15 N-put), [1,4,[8][9][10][11][12][13][14][15] N 3 ]spd ( 15 N-spd) and [1,4,8,[12][13][14][15] N 4 ]spm ( 15 N-spm) were prepared as described previously. (3-aminopropyl)cyclohexylamine (APCHA), an inhibitor of spermine synthase, were purified by the respective recrystallization of the hydrochlorides of cis/trans-4-methylcyclohexylamine and N-(3-aminopropyl)-cyclohexylamine (Ͼ98%) 11) obtained from Tokyo Kasei Kogyo, Ltd. (Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…(3-aminopropyl)cyclohexylamine (APCHA), an inhibitor of spermine synthase, were purified by the respective recrystallization of the hydrochlorides of cis/trans-4-methylcyclohexylamine and N-(3-aminopropyl)-cyclohexylamine (Ͼ98%) 11) obtained from Tokyo Kasei Kogyo, Ltd. (Tokyo, Japan). All other chemicals and organic solvents were of the purest grade available.…”

Section: Methodsmentioning

confidence: 99%

Electrospray Ionization and Time-of-Flight Mass Spectrometric Method for Simultaneous Determination of Spermidine and Spermine

Samejima

Ôtani

Murakami

et al. 2007

Biological & Pharmaceutical Bulletin

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A sensitive method for the determination of polyamines in mammalian cells was described using electrospray ionization and time-of-flight mass spectrometer. This method was 50-fold more sensitive than the previous method using ionspray ionization and quadrupole mass spectrometer. The method employed the partial purification and derivatization of polyamines, but allowed a measurement of multiple samples which contained picomol amounts of polyamines. Time required for data acquisition of one sample was approximately 2 min. The method was successfully applied for the determination of reduced spermidine and spermine contents in cultured cells under the inhibition of aminopropyltransferases. In addition, a new proper internal standard was proposed for the tracer experiment using 15 N-labeled polyamines.

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“…Fetal bovine serum (FBS) was from BioWest (Nuaill, France). Trans-4-methylcyclohexylamine (MCHA) and N-(3-aminopropyl)cyclohexylamine (APCHA) were purchased from Tokyo Chemical Industry (Tokyo, Japan) and recrystallized according to the methods in the previous reports (Shirahata et al, 1991;Kobayashi et al, 2006).…”

Section: Reagentsmentioning

confidence: 99%

“…Meanwhile Shirahata et al (1991) developed two inhibitors, trans-4-methylcyclohexylamine (MCHA) and N-(3-aminopropyl)cyclohexylamine (APCHA), which are specific to spermidine synthase and spermine synthase, respectively. The effect of MCHA and APCHA has been investigated in rats (Shirahata et al, 1993;Kobayashi et al, 2006) and mice (Chu et al, 1994) in vivo, and cultured neurons (Chu et al, 1995), rat hepatoma HC11 cells (Beppu et al, 1995), mouse mammary carcinoma FM3A cells (Nishimura et al, 2005) and malaria parasite (Haider et al, 2005) in vitro. However, there was no report regarding the effect of the two inhibitors on pancreatic beta-cells.…”

Section: Introductionmentioning

confidence: 99%

Spermidine Regulates Insulin Synthesis and Cytoplasmic Ca2+ in Mouse Beta-TC6 Insulinoma Cells

Ohtani

Mizuno

Kojima

et al. 2009

Cell Struct. Funct.

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ABSTRACT. In order to assess the functional role of the polyamines spermidine and spermine in pancreatic betacells, we examined the effect of spermidine and spermine synthase inhibitors, trans-4-methylcyclohexylamine (MCHA) and N-(3-aminopropyl)cyclohexylamine (APCHA), on cellular polyamine and insulin contents, insulin secretion, and cytoplasmic Ca 2+ concentration ([Ca 2+ ]i) in mouse insulin-secreting Beta-TC6 cells. The cellular spermidine and spermine contents were reduced 90% and 64% by cultivation of cells in the presence of MCHA and APCHA for 3 days, respectively. Addition of spermidine or spermine reversed the polyamine level reduced by MCHA or APCHA, respectively. Insulin secretion was decreased 40~60% in the cells treated with MCHA or APCHA. The reduction by MCHA was reversed to the untreated level by adding spermidine exogenously, while the effect of APCHA was not reversed by treatment with spermine. The cellular insulin content was also reduced by treatment with MCHA but not the expression of insulin 1 and 2 genes, suggesting that spermidine was involved in the translation of insulin mRNAs. The elevation of [Ca 2+ ]i, a key event triggering insulin secretion induced by glucose, was reduced in Beta-TC6 cells by MCHA treatment. The spermidine synthase inhibitor also augmented the sustained [Ca 2+ ]i rise induced by carbamylcholine but not by a high concentration of KCl or nicotine. These results suggested that spermidine rather than spermine plays an important role in the regulation of insulin synthesis and the glucose-induced [Ca 2+ ]i rise in Beta-TC6 cells.

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Inhibition of Putrescine Aminopropyltransferase Influences Rat Liver Regeneration

Cited by 6 publications

References 21 publications

Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

Electrospray Ionization and Time-of-Flight Mass Spectrometric Method for Simultaneous Determination of Spermidine and Spermine

Spermidine Regulates Insulin Synthesis and Cytoplasmic Ca2+ in Mouse Beta-TC6 Insulinoma Cells

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