caa a22 4500 397494114 CHVBK 20180308164516.0 cr unu---uuuuu 161202e199502 xx s 000 0 eng 10.1093/jb/117.2.339 doi (NATIONALLICENCE)oxford-10.1093/jb/117.2.339 Specific Depletion of Spermidine and Spermine in HTC Cells Treated with Inhibitors of Aminopropyltransferases [Elektronische Daten] [Takanobu Beppu, Akira Shirahata, Norio Takahashi, Harumi Hosoda, Keijiro Samejima] The effects of a potent spermidine synthase inhibitor, trans-4-methylcyclohexylamine (4MCHA), and a spermine synthase inhibitor, N-(3-aminopropyl)cyclohexylamine (APCHA), on polyamine biosynthesis and cell growth have been studied in rat hepatoma cells (HTC cells) in culture. Treatment of HTC cells with 4MCHA or APCHA caused a marked decrease of spermidine or spermine with a compensatory increase of putrescine and spermine or spermidine, respectively, in a dose-dependent manner, suggesting specific and potent inhibition of each target enzyme. When 250 pM 4MCHA or APCHA was administered to the cells for 8 days, spermidine was decreased to 2% of control culture or spermine below 1%, respectively, while total polyamine (sum of putrescine, spermidine, and spermine) remained almost unchanged during the culture. There were no significant changes in the growth rate during treatment with the inhibitors at 250 μM concentration. The results suggest that in the growth of cells, putrescine and spermine can be substituted for most of the fraction of cellular spermidine, and spermidine for most of the fraction of cellular spermine. Of five enzymatic activities involved in polyamine biosynthe sis and interconversion, S-adenosylmethionine decarboxylase activity increased 8-fold with 250 μM 4MCHA, and 3-fold with 250 μM APCHA during the treatment. This increase was partially due to the increase of half-life of the enzyme. Separate roles for spermidine and spermine in the biosynthesis of the enzyme protein were also suggested. © BY THE JOURNAL OF BIOCHEMISTRY Regular Papers nationallicence S-adenosylmethionine decarboxylase nationallicence cell growth nationallicence inhibitor nationallicence spermidine nationallicence spermine nationallicence Beppu Takanobu Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences Josai University, Sakado, Saitama 350-02 aut Shirahata Akira Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences Josai University, Sakado, Saitama 350-02 aut Takahashi Norio Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences Josai University, Sakado, Saitama 350-02 aut Hosoda Harumi Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences Josai University, Sakado, Saitama 350-02 aut Samejima Keijiro Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences Josai University, Sakado, Saitama 350-02 aut The Journal of Biochemistry Oxford University Press 117/2(1995-02), 339-345 0021-924X 117:2<339 1995 117 jbchem https://doi.org/10.1093/jb/117.2.339 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jb/117.2.339 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Beppu Takanobu Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences Josai University, Sakado, Saitama 350-02 aut NATIONALLICENCE 700 1- Shirahata Akira Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences Josai University, Sakado, Saitama 350-02 aut NATIONALLICENCE 700 1- Takahashi Norio Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences Josai University, Sakado, Saitama 350-02 aut NATIONALLICENCE 700 1- Hosoda Harumi Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences Josai University, Sakado, Saitama 350-02 aut NATIONALLICENCE 700 1- Samejima Keijiro Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences Josai University, Sakado, Saitama 350-02 aut NATIONALLICENCE 773 0- The Journal of Biochemistry Oxford University Press 117/2(1995-02), 339-345 0021-924X 117:2<339 1995 117 jbchem Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford