Polyamine metabolism is involved in adipogenesis of 3T3-L1 cells

Ikumi Ishii, Yoshihiko Ikeguchi, Hiroshi Mano, Masahiro Wada, Anthony E. Pegg, Akira Shirahata

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Polyamines spermidine and spermine are known to be required for mammalian cell proliferation and for embryonic development. Alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC) a limiting enzyme of polyamine biosynthesis, depleted the cellular polyamines and prevented triglyceride accumulation and differentiation in 3T3-L1 cells. In this study, to explore the function of polyamines in adipogenesis, we examined the effect of polyamine biosynthesis inhibitors on adipocyte differentiation and lipid accumulation of 3T3-L1 cells. The spermidine synthase inhibitor trans-4- methylcyclohexylamine (MCHA) increased spermine/spermidine ratios, whereas the spermine synthase inhibitor N-(3-aminopropyl)-cyclohexylamine (APCHA) decreased the ratios in the cells. MCHA was found to decrease lipid accumulation and GPDH activity during differentiation, while APCHA increased lipid accumulation and GPDH activity indicating the enhancement of differentiation. The polyamine-acetylating enzyme, spermidine/spermine N 1- acetyltransferase (SSAT) activity was increased within a few hours after stimulus for differentiation, and was found to be elevated by APCHA. In mature adipocytes APCHA decreased lipid accumulation while MCHA had the opposite effect. An acetylpolyamine oxidase and spermine oxidase inhibitor MDL72527 or an antioxidant N-acetylcysteine prevented the promoting effect of APCHA on adipogenesis. These results suggest that not only spermine/spermidine ratios but also polyamine catabolic enzyme activity may contribute to adipogenesis.

Original languageEnglish (US)
Pages (from-to)619-626
Number of pages8
JournalAmino Acids
Volume42
Issue number2-3
DOIs
StatePublished - Feb 1 2012

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3T3-L1 Cells
Adipogenesis
Polyamines
Metabolism
Spermidine
Spermine
Lipids
Biosynthesis
Adipocytes
Spermine Synthase
Spermidine Synthase
Enzymes
Eflornithine
Cell proliferation
Acetylcysteine
Enzyme activity
Embryonic Development
Oxidoreductases
Triglycerides
Antioxidants

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Ishii, I., Ikeguchi, Y., Mano, H., Wada, M., Pegg, A. E., & Shirahata, A. (2012). Polyamine metabolism is involved in adipogenesis of 3T3-L1 cells. Amino Acids, 42(2-3), 619-626. https://doi.org/10.1007/s00726-011-1037-5
Ishii, Ikumi ; Ikeguchi, Yoshihiko ; Mano, Hiroshi ; Wada, Masahiro ; Pegg, Anthony E. ; Shirahata, Akira. / Polyamine metabolism is involved in adipogenesis of 3T3-L1 cells. In: Amino Acids. 2012 ; Vol. 42, No. 2-3. pp. 619-626.
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Ishii, I, Ikeguchi, Y, Mano, H, Wada, M, Pegg, AE & Shirahata, A 2012, 'Polyamine metabolism is involved in adipogenesis of 3T3-L1 cells', Amino Acids, vol. 42, no. 2-3, pp. 619-626. https://doi.org/10.1007/s00726-011-1037-5

Polyamine metabolism is involved in adipogenesis of 3T3-L1 cells. / Ishii, Ikumi; Ikeguchi, Yoshihiko; Mano, Hiroshi; Wada, Masahiro; Pegg, Anthony E.; Shirahata, Akira.

In: Amino Acids, Vol. 42, No. 2-3, 01.02.2012, p. 619-626.

Research output: Contribution to journalArticle

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AU - Ishii, Ikumi

AU - Ikeguchi, Yoshihiko

AU - Mano, Hiroshi

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AB - Polyamines spermidine and spermine are known to be required for mammalian cell proliferation and for embryonic development. Alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC) a limiting enzyme of polyamine biosynthesis, depleted the cellular polyamines and prevented triglyceride accumulation and differentiation in 3T3-L1 cells. In this study, to explore the function of polyamines in adipogenesis, we examined the effect of polyamine biosynthesis inhibitors on adipocyte differentiation and lipid accumulation of 3T3-L1 cells. The spermidine synthase inhibitor trans-4- methylcyclohexylamine (MCHA) increased spermine/spermidine ratios, whereas the spermine synthase inhibitor N-(3-aminopropyl)-cyclohexylamine (APCHA) decreased the ratios in the cells. MCHA was found to decrease lipid accumulation and GPDH activity during differentiation, while APCHA increased lipid accumulation and GPDH activity indicating the enhancement of differentiation. The polyamine-acetylating enzyme, spermidine/spermine N 1- acetyltransferase (SSAT) activity was increased within a few hours after stimulus for differentiation, and was found to be elevated by APCHA. In mature adipocytes APCHA decreased lipid accumulation while MCHA had the opposite effect. An acetylpolyamine oxidase and spermine oxidase inhibitor MDL72527 or an antioxidant N-acetylcysteine prevented the promoting effect of APCHA on adipogenesis. These results suggest that not only spermine/spermidine ratios but also polyamine catabolic enzyme activity may contribute to adipogenesis.

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