title: Suppression of 3-deoxyglucosone and heparin-binding epidermal growth factor-like growth factor mRNA expression by an aldose reductase inhibitor in rat vascular smooth muscle cells.
abstract: Reactive carbonyl compounds and oxidative stress have been recently shown to up-regulate the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen for vascular smooth muscle cells (SMCs) produced by SMC themselves. Because the polyol pathway has been reported to influence the formation of carbonyl compounds and the oxidative stress in various cells, we conducted this study to investigate whether the polyol pathway affects HB-EGF expression along with the generation of carbonyl compounds and the oxidative stress in SMCs. We found that, compared with those cultured with 5.5mM glucose, SMCs cultured with 40 mM glucose showed the accelerated thymidine incorporation, elevated levels of intracellular sorbitol, 3-deoxyglucosone (3-DG), advanced glycation end products (AGEs), and thiobarbituric acid-reactive substances (TBARS) along with the enhanced expression of HB-EGF mRNA. An aldose reductase inhibitor (ARI), SNK-860, significantly inhibited all of these abnormalities, while aminoguanidine suppressed 3-DG levels and HB-EGF mRNA expression independent of sorbitol levels. The results suggest that the polyol pathway may play a substantial role in SMC hyperplasia under hyperglycemic condition in part by affecting HB-EGF mRNA expression via the production of carbonyl compounds and oxidative stress.
authors.affiliation: Division of Metabolic Diseases, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hamada
authors.forename: Eitaro
authors.initials: E
authors.lastname: Nakashima
authors.forename: Keiko
authors.initials: K
authors.lastname: Naruse
authors.forename: Hideki
authors.initials: H
authors.lastname: Kamiya
authors.forename: Noboru
authors.initials: N
authors.lastname: Akiyama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hirooka
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Seikoh
authors.initials: S
authors.lastname: Horiuchi
authors.forename: Nigishi
authors.initials: N
authors.lastname: Hotta
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
authors.forename: Jiro
authors.initials: J
authors.lastname: Nakamura
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013012:Sorbitol / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances; D013936:Thymidine / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D007093:Imidazoles; D048289:Imidazolidines; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D013012:Sorbitol; D004815:Epidermal Growth Factor; C077139:fidarestat; D003847:Deoxyglucose; D000449:Aldehyde Reductase; C016350:3-deoxyglucosone; D005947:Glucose; D013936:Thymidine