To examine the roles of active hypusinated eIF5A (eukaryotic translation initiation factor 5A) and polyamines in cell proliferation, mouse mammary carcinoma FM3A cells were treated with an inhibitor of deoxyhypusine synthase, GC7 (N1-guanyl-1, 7-diaminoheptane), or with an inhibitor of ornithine decarboxylase, DFMO (α-difluoromethylornithine), or with DFMO plus an inhibitor of spermine synthase, APCHA [N1-(3-aminopropyl)-cyclohexylamine]. Treatment with GC7 decreased the level of active eIF5A on day 1 without affecting cellular polyamine content, and inhibition of cell growth occurred from day 2. This delay reflects the fact that eIF5A was present in excess and was very stable in these cells. Treatment with DFMO or with DFMO plus APCHA inhibited cell growth on day 1. DFMO considerably decreased the levels of putrescine and spermidine, and the formation of active eIF5A began to decrease when the level of spermidine fell below 8 nmol/mg of protein after 12 h of incubation with DFMO. The combination of DFMO and APCHA markedly decreased the levels of putrescine and spermine and significantly decreased the level of spermidine, but did not affect the level of active eIF5A until day 3 when spermidine level decreased to 7 nmol/mg of protein. The results show that a decrease in either active eIF5A or polyamines inhibits cell growth, indicating that eIF5A and polyamines are independently involved in cell growth.
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Research Article|
January 24 2005
Independent roles of eIF5A and polyamines in cell proliferation
Kazuhiro NISHIMURA;
Kazuhiro NISHIMURA
*Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
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Kaori MUROZUMI;
Kaori MUROZUMI
*Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
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Akira SHIRAHATA;
Akira SHIRAHATA
†Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado 350-0248, Japan
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Myung Hee PARK;
Myung Hee PARK
‡Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4340, U.S.A.
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Keiko KASHIWAGI;
Keiko KASHIWAGI
*Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
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Kazuei IGARASHI
Kazuei IGARASHI
1
*Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
August 31 2004
Revision Received:
September 16 2004
Accepted:
September 17 2004
Accepted Manuscript online:
September 17 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 385 (3): 779–785.
Article history
Received:
August 31 2004
Revision Received:
September 16 2004
Accepted:
September 17 2004
Accepted Manuscript online:
September 17 2004
Citation
Kazuhiro NISHIMURA, Kaori MUROZUMI, Akira SHIRAHATA, Myung Hee PARK, Keiko KASHIWAGI, Kazuei IGARASHI; Independent roles of eIF5A and polyamines in cell proliferation. Biochem J 1 February 2005; 385 (3): 779–785. doi: https://doi.org/10.1042/BJ20041477
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