RGD Reference Report - Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals. - Rat Genome Database

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

Authors: Kurahashi, Toshihiro  Kwon, Myoungsu  Homma, Takujiro  Saito, Yuka  Lee, Jaeyong  Takahashi, Motoko  Yamada, Ken-Ichi  Miyata, Satoshi  Fujii, Junichi 
Citation: Kurahashi T, etal., Biochem Biophys Res Commun. 2014 Sep 12;452(1):136-41. doi: 10.1016/j.bbrc.2014.08.072. Epub 2014 Aug 21.
RGD ID: 13838799
Pubmed: PMID:25152401   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbrc.2014.08.072   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Akr1a1Ratcellular detoxification of aldehyde involved_inIDA PMID:25152401UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Akr1a1  (aldo-keto reductase family 1 member A1)


Additional Information