Inhibition of gene expression of heparin-binding epidermal growth factor-like growth factor by extracellular superoxide dismutase in rat aortic smooth muscle cells.
Both extracellular superoxide dismutase (EC-SOD) and heparin binding EGF like growth factor (HB-EGF) are produced in smooth muscle cells of the arterial wall, and are thought to play pathological roles in atherosclerosis with heparin binding characteristics. EC-SOD treatment clearly reduced the H2O2 induced expression of HB-EGF in rat aortic smooth muscle cells (RASMC). EC-SOD also inhibited the induction of HB-EGF by 12-O-tetradecanoylphorbol-13-acetate (TPA) in RASMC by 60%. Both H2O2 and TPA increased intracellular ROS levels, and EC-SOD inhibited ROS generation only for the case of H2O2 but not TPA. Treatment of the cells with heparin alone decreased HB-EGF expression by 20%, whereas EC-SOD alone and a co-incubation with EC-SOD and heparin suppressed the induction by 60 and 70%, respectively. These results suggest that EC-SOD is related to the EGF signaling in two ways, competition for HSPG with HB-EGF and as an ROS scavenger.
Nishimura
Masashi
M
Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Ookawara
Tomomi
T
Eguchi
Hironobu
H
Fujiwara
Noriko
N
Yoshihara
Daisaku
D
Yasuda
Jun
J
Mimura
Osamu
O
Suzuki
Keiichiro
K
D000818:Animals; D001011:Aorta / Q000166:cytology*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000235:genetics*; D005110:Extracellular Space / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*
C587884:Hbegf protein, mouse; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D006493:Heparin; D013482:Superoxide Dismutase