Aldo–keto reductase family 1 B10 protein detoxifies dietary and lipid-derived alpha, beta-unsaturated carbonyls at physiological levels

Alpha, beta-unsaturated carbonyls are highly reactive mutagens and carcinogens to which humans are exposed on a daily basis. This study demonstrates that aldo–keto reductase family 1 member B10 (AKR1B10) is a critical protein in detoxifying dietary and lipid-derived unsaturated carbonyls. Purified A...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-09, Vol.387 (2), p.245-250
Main Authors: Zhong, Linlin, Liu, Ziwen, Yan, Ruilan, Johnson, Stephen, Zhao, Yupei, Fang, Xiubin, Cao, Deliang
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Aldehyde Reductase - genetics
Aldehyde Reductase - metabolism
Aldo–keto reductase family 1 member B10
Alpha, beta-unsaturated carbonyls
BROMIDES
CARBONYLS
CARCINOGENS
Carcinogens - metabolism
Cell Line
Cytotoxicity
Cytotoxins - metabolism
Diet
FLUORESCENCE
GLUTATHIONE CONJUGATES
Glutathione-conjugated carbonyls
HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY
Humans
Inactivation, Metabolic
Intestines - enzymology
Intestines - metabolism
Lipid Metabolism
LIPIDS
MASS SPECTROSCOPY
Mutagens - metabolism
PROTEINS
Steady-state kinetics
TOXICITY
ULTRAVIOLET RADIATION
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Summary:Alpha, beta-unsaturated carbonyls are highly reactive mutagens and carcinogens to which humans are exposed on a daily basis. This study demonstrates that aldo–keto reductase family 1 member B10 (AKR1B10) is a critical protein in detoxifying dietary and lipid-derived unsaturated carbonyls. Purified AKR1B10 recombinant protein efficiently catalyzed the reduction to less toxic alcohol forms of crotonaldehyde at 0.90 μM, 4-hydroxynonenal (HNE) at 0.10 μM, trans-2-hexanal at 0.10 μM, and trans-2,4-hexadienal at 0.05 μM, the concentrations at or lower than physiological exposures. Ectopically expressed AKR1B10 in 293T cells eliminated immediately HNE at 1 (subtoxic) or 5 μM (toxic) by converting to 1,4-dihydroxynonene, protecting the cells from HNE toxicity. AKR1B10 protein also showed strong enzymatic activity toward glutathione-conjugated carbonyls. Taken together, our study results suggest that AKR1B10 specifically expressed in the intestine is physiologically important in protecting the host cell against dietary and lipid-derived cytotoxic carbonyls.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2009.06.123