Overexpression of Cu/Zn-superoxide dismutase and/or catalase in mice inhibits aorta smooth muscle cell proliferation.
BACKGROUND
Increasing evidence demonstrates that reactive oxygen species, for example, superoxide (O(2)(-.)) and hydrogen peroxide (H(2)O(2)), promote vascular smooth muscle cell (VSMC) proliferation, and that superoxide dismutase (SOD) and catalase work in concert to scavenge O(2)(-.) and H(2)O(2). This report examined the effect of overexpressing Cu/Zn-SOD or catalase on epidermal growth factor (EGF)-induced proliferation and mitogen-activated protein kinase (MAPK) phosphorylation in VSMCs.


METHODS
The VSMCs were obtained from the aorta of wild-type mice and transgenic mice overexpressing Cu/Zn-SOD and catalase in combination or overexpressing Cu/Zn-SOD or catalase alone. The VSMC proliferation was measured by cell counting and bromodeoxyuridine incorporation assay. The MAPK phosphorylation was determined with Western blotting.


RESULTS
Treatment of wild-type VSMCs with EGF significantly increased proliferation and phosphorylation of extracellular signal-regulated kinases (ERK1/2) and p38 MAPK. Overexpression of Cu/Zn-SOD or catalase attenuated EGF-induced phosphorylation of ERK1/2 and p38 MAPK and suppressed EGF-induced proliferation in VSMCs. For example, the EGF-induced phosphorylation of ERK1/2 and p38 MAPK and EGF-induced proliferation in VSMCs overexpressing Cu/Zn-SOD or catalase were significantly less than in wild-type VSMCs. Moreover, VSMCs overexpressing Cu/Zn-SOD and catalase in combination showed significantly less proliferation and less phosphorylation of the MAPKs than those overexpressing Cu/Zn-SOD or catalase alone.


CONCLUSIONS
Overexpression of Cu/Zn-SOD and catalase in combination is more efficient in inhibiting VSMC proliferation and MAPK phosphorylation than overexpression of Cu/Zn-SOD or catalase alone.
Shi
MingJian
M
Department of Pathology, Anatomy & Cell Biology, Meharry Medical College, Nashville, TN 37208, USA.
Yang
Hong
H
Motley
Evangeline D
ED
Guo
ZhongMao
Z
D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000378:metabolism*; D002374:Catalase / Q000096:biosynthesis*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D017382:Reactive Oxygen Species; D013481:Superoxides; D004815:Epidermal Growth Factor; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases