Overexpression of Cu/Zn-superoxide dismutase and/or catalase in mice inhibits aorta smooth muscle cell proliferation

Abstract

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.