Rabbit extracellular superoxide dismutase: expression and effect on LDL oxidation

Extracellular superoxide dismutase (EC-SOD) is a secreted antioxidative enz yme with an abundant mRNA expression in kidney and arterial wail. In order to study expression and antioxidative function of EC-SOD, we cloned the rab bit ec-sod cDNA and produced the recombinant protein in cell culture. In vi tro studies did not show a direct relationship between the amounts of synth esized mRNA and secreted protein activity, suggesting post-transcriptional regulation. The antiatherogenic role of EC-SOD was studied by determining t he effect of EC-SOD on the oxidation (ox) of low density lipoprotein (LDL), and subsequent degradation of oxLDL in RAW 264 macrophages in vitro. It wa s found that resombinant EC-SOD reduced both the degradation of LDL in RAW 264 macrophages by 28-36% and its electrophoretic mobility caused by endoth elial cell-mediated oxidation. It is therefore suggested that EC-SOD can ac t as a protective enzyme against the development of atherosclerosis. (C) 20 00 Elsevier Science B.V. All rights reserved.