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Increased sensitivity of homozygous Sod2 mutant mice to oxygen toxicity.
Free Radic Biol Med. 2002 Jan 15; 32(2):175-86.FR

Abstract

Induction or overexpression of pulmonary manganese superoxide dismutase (MnSOD) has been shown to protect against oxygen (O2) toxicity. Genetic inactivation of MnSOD (Sod2) results in multiple organ failure and early neonatal death. However, lungs or O2-tolerance of Sod2 knockout mice have not been investigated. We evaluated survival, lung histopathology, and other pulmonary antioxidants (glutathione cycle) of homozygous (-/-) and heterozygous (+/-) Sod2 mutant mice compared with wild-type controls (Sod2+/+) following 48 h exposure to either room air or to O2. The ability of antioxidant N-acetylcysteine to compensate for the loss of MnSOD was explored. Mortality of Sod2-/- mice increased from 0% in room air to 18 and 83% in 50 and 80% O2, respectively. N-acetylcysteine did not alter mortality of Sod2-/- mice. Histopathological analysis revealed abnormalities in saccules of Sod2-/- mice exposed either to room air or to 50% O2 suggestive of delayed postnatal lung development. In 50% O2, activities of glutamate-cysteine ligase (GCL) (previously known as gamma-glutamylcysteine synthetase, gamma-GCS) and glutathione peroxidase increased in Sod2-/- (35 and 70%, respectively) and Sod2+/- (12 and 70%, respectively) mice, but glutathione levels remained unaltered. We conclude that MnSOD is required for normal O2 tolerance and that in the absence of MnSOD there is a compensatory increase in pulmonary glutathione-dependent antioxidant defense in hyperoxia.

Authors+Show Affiliations

Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. tiina.asikainen@hus.fiNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11796207

Citation

Asikainen, Tiina M., et al. "Increased Sensitivity of Homozygous Sod2 Mutant Mice to Oxygen Toxicity." Free Radical Biology & Medicine, vol. 32, no. 2, 2002, pp. 175-86.
Asikainen TM, Huang TT, Taskinen E, et al. Increased sensitivity of homozygous Sod2 mutant mice to oxygen toxicity. Free Radic Biol Med. 2002;32(2):175-86.
Asikainen, T. M., Huang, T. T., Taskinen, E., Levonen, A. L., Carlson, E., Lapatto, R., Epstein, C. J., & Raivio, K. O. (2002). Increased sensitivity of homozygous Sod2 mutant mice to oxygen toxicity. Free Radical Biology & Medicine, 32(2), 175-86.
Asikainen TM, et al. Increased Sensitivity of Homozygous Sod2 Mutant Mice to Oxygen Toxicity. Free Radic Biol Med. 2002 Jan 15;32(2):175-86. PubMed PMID: 11796207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased sensitivity of homozygous Sod2 mutant mice to oxygen toxicity. AU - Asikainen,Tiina M, AU - Huang,Ting-Ting, AU - Taskinen,Eero, AU - Levonen,Anna-Liisa, AU - Carlson,Elaine, AU - Lapatto,Risto, AU - Epstein,Charles J, AU - Raivio,Kari O, PY - 2002/2/14/pubmed PY - 2002/3/28/medline PY - 2002/2/14/entrez SP - 175 EP - 86 JF - Free radical biology & medicine JO - Free Radic. Biol. Med. VL - 32 IS - 2 N2 - Induction or overexpression of pulmonary manganese superoxide dismutase (MnSOD) has been shown to protect against oxygen (O2) toxicity. Genetic inactivation of MnSOD (Sod2) results in multiple organ failure and early neonatal death. However, lungs or O2-tolerance of Sod2 knockout mice have not been investigated. We evaluated survival, lung histopathology, and other pulmonary antioxidants (glutathione cycle) of homozygous (-/-) and heterozygous (+/-) Sod2 mutant mice compared with wild-type controls (Sod2+/+) following 48 h exposure to either room air or to O2. The ability of antioxidant N-acetylcysteine to compensate for the loss of MnSOD was explored. Mortality of Sod2-/- mice increased from 0% in room air to 18 and 83% in 50 and 80% O2, respectively. N-acetylcysteine did not alter mortality of Sod2-/- mice. Histopathological analysis revealed abnormalities in saccules of Sod2-/- mice exposed either to room air or to 50% O2 suggestive of delayed postnatal lung development. In 50% O2, activities of glutamate-cysteine ligase (GCL) (previously known as gamma-glutamylcysteine synthetase, gamma-GCS) and glutathione peroxidase increased in Sod2-/- (35 and 70%, respectively) and Sod2+/- (12 and 70%, respectively) mice, but glutathione levels remained unaltered. We conclude that MnSOD is required for normal O2 tolerance and that in the absence of MnSOD there is a compensatory increase in pulmonary glutathione-dependent antioxidant defense in hyperoxia. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/11796207/Increased_sensitivity_of_homozygous_Sod2_mutant_mice_to_oxygen_toxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891584901007766 DB - PRIME DP - Unbound Medicine ER -