Properties and tissue distribution of a novel aldo-keto reductase encoding in a rat gene (Akr1b10).
A recent rat genomic sequencing predicts a gene Akr1b10 that encodes a protein with 83% sequence similarity to human aldo-keto reductase (AKR) 1B10. In this study, we isolated the cDNA for the rat AKR1B10 (R1B10) from rat brain, and examined the enzymatic properties of the recombinant protein. R1B10 utilized NADPH as the preferable coenzyme, and reduced various aldehydes (including cytotoxic 4-hydroxy-2-hexenal and 4-hydroxy- and 4-oxo-2-nonenals) and α-dicarbonyl compounds (such as methylglyoxal and 3-deoxyglucosone), showing low K(m) values of 0.8-6.1μM and 3.7-67μM, respectively. The enzyme also reduced glyceraldehyde and tetroses (K(m)=96-390μM), although hexoses and pentoses were inactive and poor substrates, respectively. Among the substrates, 4-oxo-2-nonenal was most efficiently reduced into 4-oxo-2-nonenol, and its cytotoxicity against bovine endothelial cells was decreased by the overexpression of R1B10. R1B10 showed low sensitivity to aldose reductase inhibitors, and was activated to approximately two folds by valproic acid, and alicyclic and aromatic carboxylic acids. The mRNA for R1B10 was expressed highly in rat brain and heart, and at low levels in other rat tissues and skin fibroblasts. The results suggest that R1B10 functions as a defense system against oxidative stress and glycation in rat tissues.
Endo
Satoshi
S
Gifu Pharmaceutical University, Japan. sendo@gifu-pu.ac.jp
Matsunaga
Toshiyuki
T
Kuragano
Tsukasa
T
Ohno
Satoshi
S
Kitade
Yukio
Y
Tajima
Kazuo
K
El-Kabbani
Ossama
O
Hara
Akira
A
D000449:Aldehyde Reductase / Q000737:chemistry* / Q000235:genetics; D000447:Aldehydes / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D000818:Animals; D001921:Brain; D001923:Brain Chemistry; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005796:Genes; D006801:Humans; D007700:Kinetics; D008297:Male; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism*; D013379:Substrate Specificity; D014018:Tissue Distribution / Q000235:genetics
D000447:Aldehydes; D018076:DNA, Complementary; D011994:Recombinant Proteins; C045934:4-hydroxy-2-hexenal; D009249:NADP; D003847:Deoxyglucose; C120471:AKR1B10 protein, human; C553248:Akr1b10 protein, rat; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; C016350:3-deoxyglucosone