title: Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kurahashi
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Myoungsu
authors.initials: M
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Takujiro
authors.initials: T
authors.lastname: Homma
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Jaeyong
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Bio-functional Science, Faculty of Pharmacological Science, Kyushu University, Fukuoka, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Internal Medicine, Osaka Hospital, Japan Community Health Care Organization, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyata
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Fujii
mesh_terms: D000171:Acrolein / Q000493:pharmacokinetics* / Q000633:toxicity; D000449:Aldehyde Reductase / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D008658:Inactivation, Metabolic; D051379:Mice
chemical_list: D000171:Acrolein; D000449:Aldehyde Reductase
keywords: Acrolein; Aldehyde reductase; Ascorbic acid; Detoxification; Mouse embryonic fibroblast