| First Author | Ueda J | Year | 2008 |
| Journal | Free Radic Biol Med | Volume | 45 |
| Issue | 6 | Pages | 897-904 |
| PubMed ID | 18640266 | Mgi Jnum | J:142003 |
| Mgi Id | MGI:3820174 | Doi | 10.1016/j.freeradbiomed.2008.06.016 |
| Citation | Ueda J, et al. (2008) Decreased pulmonary extracellular superoxide dismutase during systemic inflammation. Free Radic Biol Med 45(6):897-904 |
| abstractText | Oxidative damage is a major cause of lung injury during systemic inflammatory response syndrome. In this study, the expression of an antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), and its protective role against pulmonary oxidative damage were investigated using mouse models of systemic inflammation. Intraperitoneal injection with bacterial endotoxin lipopolysaccharides (LPS; 20 mg/kg) caused oxidative damage in lungs as assessed by increased tyrosine nitration in proteins. LPS administration also resulted in a rapid and significant loss of more than 80% of pulmonary EC-SOD in a time- and dose-dependent manner, but other types of SODs, cytoplasmic CuZn-SOD and mitochondrial Mn-SOD, were not affected. EC-SOD protein is most abundant in lungs but also present at high levels in other tissues such as heart and white fat; however, the LPS-mediated decrease in this enzyme was most apparent in the lungs. Intravenous injection of mice with tumor necrosis factor alpha (10 microg per mouse) also caused a 60% decrease in EC-SOD in the lungs, suggesting that the EC-SOD down-regulation is mediated by this LPS-inducible inflammatory cytokine. A protective role for EC-SOD against LPS-mediated systemic inflammation was shown by an increased survival rate (75% vs 29% in 5 days) and decreased pulmonary oxidative damage in EC-SOD transgenic mice that overexpress the human EC-SOD gene. These results demonstrate that the inflammation-mediated EC-SOD down-regulation has a major pathophysiological impact during the systemic inflammatory response syndrome. |
