TY - JOUR
T1 - Characterization of a rat NADPH-dependent aldo-keto reductase (AKR1B13) induced by oxidative stress
AU - Endo, Satoshi
AU - Matsunaga, Toshiyuki
AU - Mamiya, Hiroaki
AU - Hara, Akira
AU - Kitade, Yukio
AU - Tajima, Kazuo
AU - El-Kabbani, Ossama
PY - 2009
Y1 - 2009
N2 - A rat aldo-keto reductase (AKR1B13) was identified as a hepatoma-derived protein, exhibiting high sequence identity with Mouse fibroblast growth factor (FGF)-induced reductase, AKR1B8. In this study, AKR1B13 was characterized in terms of its enzymatic properties, tissue distribution and regulation. Recombinant AKR1B13 exhibited NADPH-linked reductase activity towards various aldehydes and alpha-dicarbonyl compounds, which include reactive compounds such as methylglyoxal, glyoxal, acrolein, 4-hydroxynonenal and 3-deoxyglucosone. The enzyme exhibited low NADP(+)-linked dehydrogenase activity towards aliphatic and aromatic alcohols, and was inhibited by aldose reductase inhibitors, flavonoids, benzbromarone and hexestrol. Immunochemical and reverse transcription-PCR analyses revealed that the enzyme is expressed in many rat tissues, endothelial cells and fibroblasts. Gene expression in YPEN-1 and NRK cells was Lip-regulated by treatments with submicromolar concentrations of hydrogen peroxide and 1,4-naphthoquinone, but not with FGF-1, FGF-2, 5 alpha-dihydrotestosterone and 17 beta-estradiol. These results indicate that AKR1B13 differs from AKR1B8 in tissue distribution and gene regulation, and suggest that it functions as a defense system against oxidative stress in rat tissues. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
AB - A rat aldo-keto reductase (AKR1B13) was identified as a hepatoma-derived protein, exhibiting high sequence identity with Mouse fibroblast growth factor (FGF)-induced reductase, AKR1B8. In this study, AKR1B13 was characterized in terms of its enzymatic properties, tissue distribution and regulation. Recombinant AKR1B13 exhibited NADPH-linked reductase activity towards various aldehydes and alpha-dicarbonyl compounds, which include reactive compounds such as methylglyoxal, glyoxal, acrolein, 4-hydroxynonenal and 3-deoxyglucosone. The enzyme exhibited low NADP(+)-linked dehydrogenase activity towards aliphatic and aromatic alcohols, and was inhibited by aldose reductase inhibitors, flavonoids, benzbromarone and hexestrol. Immunochemical and reverse transcription-PCR analyses revealed that the enzyme is expressed in many rat tissues, endothelial cells and fibroblasts. Gene expression in YPEN-1 and NRK cells was Lip-regulated by treatments with submicromolar concentrations of hydrogen peroxide and 1,4-naphthoquinone, but not with FGF-1, FGF-2, 5 alpha-dihydrotestosterone and 17 beta-estradiol. These results indicate that AKR1B13 differs from AKR1B8 in tissue distribution and gene regulation, and suggest that it functions as a defense system against oxidative stress in rat tissues. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
UR - http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T56-4TGHNG2-6&_user=542840&_coverDate=03%2F16%2F2009&_rdoc=1&_fmt=high&_orig=search&_sort=d
M3 - Article
SN - 0009-2797
VL - 178
SP - 151
EP - 157
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
IS - 1-3
ER -