title: Induction of thioredoxin reductase as an adaptive response to acrolein in human umbilical vein endothelial cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, Graduate School of Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yong Seek
authors.initials: YS
authors.lastname: Park
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Misonou
authors.forename: Noriko
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Motoko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Koh
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: 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*
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D000171:Acrolein; D003513:Cycloheximide; D013880:Thioredoxin-Disulfide Reductase; D000111:Acetylcysteine