Decrease in acrolein toxicity based on the decline of polyamine oxidases

Takeshi Uemura, Mizuho Nakamura, Akihiko Sakamoto, Takehiro Suzuki, Naoshi Dohmae, Yusuke Terui, Hideyuki Tomitori, Robert A Casero, Keiko Kashiwagi, Kazuei Igarashi

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Abstract

We have shown recently that acrolein is strongly involved in cell damage during brain infarction and chronic renal failure. To study the mechanism of acrolein detoxification, we tried to isolate Neuro2a cells with reduced sensitivity to acrolein toxicity (Neuro2a-ATD cells). In one cell line, Neuro2a-ATD1, the level of glutathione (GSH) was increased. We recently isolated a second cell line, Neuro2a-ATD2, and found that acrolein-producing enzymes [polyamine oxidases (PAO); i.e. acetylpolyamine oxidase (AcPAO), and spermine oxidase (SMO)] are reduced in this cell line due to changes at the level of transcription. In the Neuro2a-ATD2 cells, the IC50 of acrolein increased from 4.2 to 6.8 μM, and the levels of FosB and C/EBPβ — transcription factors involved in the transcription of AcPAO and SMO genes — were reduced. Transfection of siRNAs for FosB and C/EBPβ reduced the levels of AcPAO and SMO, respectively. In addition, the synthesis of FosB and AcPAO was also decreased by siRNA for C/EBPβ, because C/EBPβ is one of the transcription factors for the FosB gene. It was also found that transfection of siRNA for C/EBPβ decreased SMO promoter activity in Neuro2a cells but not in ATD2 cells confirming that a decrease in C/EBPβ is involved in the reduced SMO activity in Neuro2a-ATD2 cells. Furthermore, transfection of the cDNA for AcPAO or SMO into Neuro2a cells increased the toxicity of acrolein. These results suggest that acrolein is mainly produced from polyamines by PAO.

Original languageEnglish (US)
Pages (from-to)151-157
Number of pages7
JournalInternational Journal of Biochemistry and Cell Biology
Volume79
DOIs
StatePublished - Oct 1 2016

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Keywords

  • Acrolein toxicity-decreasing cells
  • AP-1 (FosB and JunB) transcription factors
  • C/EBPβ transcription factor
  • Glutathione
  • Polyamine oxidases
  • Polyamines

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Uemura, T., Nakamura, M., Sakamoto, A., Suzuki, T., Dohmae, N., Terui, Y., Tomitori, H., Casero, R. A., Kashiwagi, K., & Igarashi, K. (2016). Decrease in acrolein toxicity based on the decline of polyamine oxidases. International Journal of Biochemistry and Cell Biology, 79, 151-157. https://doi.org/10.1016/j.biocel.2016.08.039