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Survival, lung injury, and lung protein nitration in heterozygous MnSOD knockout mice in hyperoxia
R M Jackson1, E S Helton, L Viera
1Birmingham DVAMC, Alabama, USA. rjackson@uab.edu
Abstract:
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.
Insights
Mice with reduced manganese superoxide dismutase (MnSOD) activity showed similar lung injury and survival rates when exposed to hyperoxia compared to wild-type mice. This suggests MnSOD is not critical for protecting against acute oxygen toxicity in this model.
Area of Science:
- Biochemistry
- Physiology
- Toxicology
Background:
- Superoxide dismutase (SOD) enzymes are crucial for cellular defense against reactive oxygen species.
- Manganese superoxide dismutase (MnSOD) is a key antioxidant enzyme found in mitochondria.
- Understanding the role of MnSOD in hyperoxia-induced lung injury is important for developing therapeutic strategies.
Purpose of the Study:
- To investigate the impact of heterozygous MnSOD knockout on mouse survival and lung injury under hyperoxia.
- To compare the response of MnSOD-deficient mice to wild-type mice when exposed to varying oxygen concentrations.
Main Methods:
- Heterozygous MnSOD knockout mice and wild-type littermates were exposed to lethal (85-100% oxygen) and sublethal (50-75% oxygen) hyperoxia.
- Survival rates, lung injury markers (protein concentration, neutrophil infiltration, wet/dry weight ratio), and biochemical parameters were assessed.
- Immunohistochemistry was used to detect protein nitration.
Main Results:
- Heterozygous MnSOD knockout mice exhibited significantly reduced lung MnSOD and catalase activity but similar total SOD activity.
- No significant differences in survival or lung injury markers were observed between genotypes under lethal or sublethal hyperoxia.
- Hyperoxia similarly increased lung injury and protein nitration in both heterozygous and wild-type mice.
Conclusions:
- Reduced MnSOD activity alone does not confer increased susceptibility to acute hyperoxia-induced lung injury in mice.
- Other antioxidant systems may compensate for the deficiency in MnSOD under these conditions.
- Further research is needed to elucidate the specific roles of different SOD isoforms in oxygen toxicity.