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Decrease in acrolein toxicity based on the decline of polyamine oxidases

delete2016-10-01
delete13
PRE
AI
T
Takeshi Uemura
M
Mizuho Nakamura
A
Akihiko Sakamoto
T
Takehiro Suzuki
N
Naoshi Dohmae
Y
Yusuke Terui
R
Robert A. Casero
K
Kazuei Igarashi *
DOI:10.1016/j.biocel.2016.08.039delete
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Abstract

Abstract

En 中文
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 M, and the levels of FosB and C/EBP beta - transcription factors involved in the transcription of AcPAO and SMO genes were reduced. Transfection of siRNAs for FosB and C/EBPp reduced the levels of AcPAO and SMO, respectively. In addition, the synthesis of FosB and AcPAO was also decreased by siRNA for C/EBP beta, because C/EBP beta is one of the transcription factors for the FosB gene. It was also found that transfection of siRNA for C/EBPp decreased SMO promoter activity in Neuro2a cells but not in ATD2 cells confirming that a decrease in C/EBP[3 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. (C) 2016 Elsevier Ltd. All rights reserved.
Keywords:
Acrolein toxicity-decreasing cells
Glutathione
Polyamines
Polyamine oxidases
AP-1 (FosB and JunB) transcription factors
C/EBP beta transcription factor

Journal

I
International Journal of Biochemistry and Cell Biology
IF:
2.8
Papers:
5.9K
Citations:
1.6W

Organization

J
Johns Hopkins University
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3.3K
Papers: 1.1K
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C
chiba university
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467
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R
RIKEN
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269
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Citations: 1.8K
J
johns hopkins medicine
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141
Papers: 88
Citations: 1.6K
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