title: The internalization and metabolism of 3-deoxyglucosone in human umbilical vein endothelial cells.
abstract: 3-Deoxyglucosone (3-DG), a dicarbonyl compound produced by glycation, plays a role in the modification and cross-linking of long-lived proteins. We synthesized [3H]3-DG from [3H]glucose and developed an internalization assay system using HPLC to examine its cellular metabolism. When smooth muscle cells or human umbilical vein endothelial cells were incubated with [3H]3-DG, it was found that [3H]3-DG was internalized by cells in a time dependent manner. The rate of internalization was reduced when the cells were incubated at 4 degrees C or treated with phenylarsine oxide (PAO). By monitoring [3H]3-DG taken up by cells, it was confirmed that 3-DG is reduced to 3-deoxyfructose (3-DF) and that this reaction was inhibited by an aldo-keto reductase inhibitor (ARI). The presence of 3-DG led to an increase in reactive oxygen species levels in the cells and subsequent apoptosis, and the effect was enhanced by pretreatment with ARI. These results suggest that 3-DG is internalized by cells and reduced to 3-DF by aldo-keto reductases, and that the internalized 3-DG is responsible for the production of intracellular oxidative stress.
authors.affiliation: Department of Biochemistry, Osaka University Graduate School of Medicine, B1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sakiyama
authors.forename: Motoko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Teshima
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Misonou
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D002478:Cells, Cultured; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014316:Tritium; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D014316:Tritium; D003847:Deoxyglucose; C016350:3-deoxyglucosone