Induction of thioredoxin reductase as an adaptive response to acrolein in human umbilical vein endothelial cells.
Acrolein is a highly electrophilic alpha,beta-unsaturated aldehyde to which humans are exposed in a variety of environment situations and is also a product of lipid peroxidation. Increased unsaturated aldehyde levels and reduced antioxidant status play an important role in the pathogenesis of a number of human diseases such as Alzheimer's, atherosclerosis, and diabetes. Mammalian thioredoxin reductase (TR), a central antioxidant enzyme, is a selenoprotein that catalyzes the reduction of oxidized thioredoxin. The findings reported here show that low concentrations of acrolein rapidly inactivate TR, both in vitro and in vivo. These data suggest that acrolein may directly inactivate TR, resulting in an increase in oxidative cellular damage. In addition, we also found that the initial inactivation of TR molecules by acrolein triggers a compensatory signal for inducing TR gene expression in human umbilical vein endothelial cells (HUVEC). The results of the present study suggest that HUVEC may have a protective system against cell damage by acrolein via the upregulation of TR, which is an adaptive response to oxidative stress.
Park
Yong Seek
YS
Department of Biochemistry, Graduate School of Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Misonou
Yoshiko
Y
Fujiwara
Noriko
N
Takahashi
Motoko
M
Miyamoto
Yasuhide
Y
Koh
Young Ho
YH
Suzuki
Keiichiro
K
Taniguchi
Naoyuki
N
D000111:Acetylcysteine / Q000494:pharmacology; D000171:Acrolein / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology*
D000975:Antioxidants; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D000171:Acrolein; D003513:Cycloheximide; D013880:Thioredoxin-Disulfide Reductase; D000111:Acetylcysteine