Survival, lung injury, and lung protein nitration in heterozygous MnSOD knockout mice in hyperoxia.
This study tested whether a strain of heterozygous Mn superoxide dismutase (SOD) knockout mice differed from wild types in response to lethal (100 or 85%) or sublethal (50 or 75%) oxygen exposures. Lung MnSOD activity was significantly (-40%) less in the heterozygous mice, and lung catalase activity was also significantly decreased. Total SOD activity, glutathione peroxidase, and glutathione reductase did not differ between heterozygous (+/-) and wild-type (+/+) mice. We exposed both heterozygous and wild-type mice to hyperoxia (50, 75, 85, or 100% oxygen) until death or for 48 hours to assess sublethal lung injury. Survival of the heterozygous and wild-type mice did not differ significantly in 100 or 85% oxygen. No mice of either genotype died in 50 or 75% oxygen (14-day exposures). Hyperoxia exposures significantly increased (by two-way ANOVA) the alveolar lavage protein concentration, percent neutrophils, and lung wet-dry/dry weight ratios. No significant differences occurred between the heterozygous and wild-type mice for any marker of injury at any oxygen level. Lavage fluid total nitrite concentrations did not differ at any oxygen level. Hyperoxia caused a similar degree of nitration of lung structural proteins detected by immunohistochemistry in both groups.
Jackson
R M
RM
Birmingham DVAMC, Alabama, USA. rjackson@uab.edu
Helton
E S
ES
Viera
L
L
Ohman
T
T
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006579:Heterozygote; D018496:Hyperoxia / Q000235:genetics / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D055370:Lung Injury; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism*; D010641:Phenotype; D011506:Proteins / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D009566:Nitrates; D011506:Proteins; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase