Enhanced bleomycin-induced pulmonary damage in mice lacking extracellular superoxide dismutase.
Extracellular superoxide dismutase (EC-SOD) is highly expressed in the extracellular matrix of lung and vascular tissue. Localization of EC-SOD to the matrix of the lung may protect against oxidative tissue damage that leads to pulmonary fibrosis. This study directly examines the protective role of EC-SOD in a bleomycin model of pulmonary fibrosis and the effect of this enzyme on oxidative protein fragmentation. Mice null for ec-sod display a marked increase in lung inflammation at 14 d post-bleomycin treatment as compared to their wild-type counterparts. Hydroxyproline analysis determined that both wild-type and ec-sod null mice display a marked increase in interstitial fibrosis at 14 d post-treatment, and the severity of fibrosis is significantly increased in ec-sod null mice compared to wild-type mice. To determine if the lack of EC-SOD promotes bleomycin-induced oxidative protein modification, 2-pyrrolidone content (as a measure of oxidative protein fragmentation at proline residues) was assessed in lung tissue from treated mice. 2-Pyrrolidone levels in the lung hydrolysates from ec-sod null mice were increased at both 7 and 14 d post-bleomycin treatment as compared to wild-type mice, indicating EC-SOD can inhibit oxidative fragmentation of proteins in this specific model of oxidative stress.
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Cheryl L
CL
Fattman
Ling-Yi
LY
Chang
Toni A
TA
Termin
Louise
L
Petersen
Jan J
JJ
Enghild
Tim D
TD
Oury
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000201:enzymology*; D006909:Hydroxyproline / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D008171:Lung Diseases / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D011760:Pyrrolidinones / Q000032:analysis; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000378:metabolism
D024042:Collagen Type I; D011760:Pyrrolidinones; D001761:Bleomycin; D013482:Superoxide Dismutase; C028537:2-pyrrolidone; D006909:Hydroxyproline