Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals

Toshihiro Kurahashi, Myoungsu Kwon, Takujiro Homma, Yuka Saito, Jaeyong Lee, Motoko Takahashi, Ken-Ichi Yamada, Satoshi Miyata, Junichi Fujii

研究成果: ジャーナルへの寄稿記事

12 引用 (Scopus)

抄録

Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, suppresses diabetic complications via a reduction in metabolic intermediates; it also plays a role in ascorbic acid biosynthesis in mice. Because primates cannot synthesize ascorbic acid, a principle role of AKR1A appears to be the reductive detoxification of aldehydes. In this study, we isolated and immortalized mouse embryonic fibroblasts (MEFs) from wild-type (WT) and human Akr1a-transgenic (Tg) mice and used them to investigate the potential roles of AKR1A under culture conditions. Tg MEFs showed higher methylglyoxal- and acrolein-reducing activities than WT MEFs and also were more resistant to cytotoxicity. Enzymatic analyses of purified rat AKR1A showed that the efficiency of the acrolein reduction was about 20% that of glyceraldehyde. Ascorbic acid levels were quite low in the MEFs, and while the administration of ascorbic acid to the cells increased the intracellular levels of ascorbic acid, it had no affect on the resistance to acrolein. Endoplasmic reticulum stress and protein carbonylation induced by acrolein treatment were less evident in Tg MEFs than in WT MEFs. These data collectively indicate that one of the principle roles of AKR1A in primates is the reductive detoxification of aldehydes, notably acrolein, and protection from its detrimental effects.

元の言語英語
ページ(範囲)136-141
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
452
発行部数1
DOI
出版物ステータス出版済み - 9 12 2014

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Acrolein
Aldehyde Reductase
Detoxification
Mammals
Fibroblasts
Ascorbic Acid
Transgenic Mice
Aldehydes
Primates
Protein Carbonylation
Glyceraldehyde
Pyruvaldehyde
Carbonylation
Endoplasmic Reticulum Stress
Biosynthesis
Diabetes Complications
Cytotoxicity
Heat-Shock Proteins
Cell culture
Rats

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals. / Kurahashi, Toshihiro; Kwon, Myoungsu; Homma, Takujiro; Saito, Yuka; Lee, Jaeyong; Takahashi, Motoko; Yamada, Ken-Ichi; Miyata, Satoshi; Fujii, Junichi.

:: Biochemical and Biophysical Research Communications, 巻 452, 番号 1, 12.09.2014, p. 136-141.

研究成果: ジャーナルへの寄稿記事

Kurahashi, Toshihiro ; Kwon, Myoungsu ; Homma, Takujiro ; Saito, Yuka ; Lee, Jaeyong ; Takahashi, Motoko ; Yamada, Ken-Ichi ; Miyata, Satoshi ; Fujii, Junichi. / Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals. :: Biochemical and Biophysical Research Communications. 2014 ; 巻 452, 番号 1. pp. 136-141.
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abstract = "Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, suppresses diabetic complications via a reduction in metabolic intermediates; it also plays a role in ascorbic acid biosynthesis in mice. Because primates cannot synthesize ascorbic acid, a principle role of AKR1A appears to be the reductive detoxification of aldehydes. In this study, we isolated and immortalized mouse embryonic fibroblasts (MEFs) from wild-type (WT) and human Akr1a-transgenic (Tg) mice and used them to investigate the potential roles of AKR1A under culture conditions. Tg MEFs showed higher methylglyoxal- and acrolein-reducing activities than WT MEFs and also were more resistant to cytotoxicity. Enzymatic analyses of purified rat AKR1A showed that the efficiency of the acrolein reduction was about 20{\%} that of glyceraldehyde. Ascorbic acid levels were quite low in the MEFs, and while the administration of ascorbic acid to the cells increased the intracellular levels of ascorbic acid, it had no affect on the resistance to acrolein. Endoplasmic reticulum stress and protein carbonylation induced by acrolein treatment were less evident in Tg MEFs than in WT MEFs. These data collectively indicate that one of the principle roles of AKR1A in primates is the reductive detoxification of aldehydes, notably acrolein, and protection from its detrimental effects.",
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