Am. J. Respir. Cell Mol. Biol., Volume 19, Number 1, July, 1998 114-120

Susceptibility of Heterozygous MnSOD Gene-Knockout Mice to Oxygen Toxicity

Min-Fu Tsan, Julie E. White, Barbara Caska, Charles J. Epstein, and C. Y. Lee

Research and Laboratory Services, Samuel S. Stratton Department of Veterans Affairs Medical Center; Departments of Physiology, Medicine, Pathology, and Laboratory Medicine, Albany Medical College, Albany, New York; and Department of Pediatrics, University of California, San Francisco, California

Recent studies have shown that homozygous Mn superoxide dismutase (Sod2) gene-knockout mice (Sod2^/) die shortly after birth with extensive myocardial injury, whereas heterozygous mutants (Sod2^+/) are phenotypically normal in room air. In the current study, we showed that Sod2^+/ mice with approximately 50% of normal pulmonary MnSOD activity and normal levels of lung CuZnSOD, catalase, and glutathione peroxidase activities were not substantially more susceptible to 100% O₂ toxicity than their normal Sod2^+/+ littermates. The mean (± SD) survival of Sod2^+/ mice in 100% O₂ was 101.4 ± 14.8 h (n = 20) versus 103.2 ± 11.3 h (n = 20) for Sod2^+/+ littermates (P > 0.60). In addition, Sod2^+/ mice with approximately 50% of normal heart MnSOD activity and Sod2^+/+ mice did not develop any ultrastructural abnormalities in the myocardium at 75 h or 90 h after 100% O₂ exposure. These results suggest that in mice, only 50% of MnSOD activity may be sufficient for normal resistance to 100% O₂ toxicity.

This article has been cited by other articles:

				D. R. Prows, A. P. Hafertepen, W. J. Gibbons Jr., A. V. Winterberg, and T. G. Nick A genetic mouse model to investigate hyperoxic acute lung injury survival Physiol Genomics, August 20, 2007; 30(3): 262 - 270. [Abstract] [Full Text] [PDF]

				X. Yi and N. Maeda Endogenous Production of Lipoic Acid Is Essential for Mouse Development Mol. Cell. Biol., September 15, 2005; 25(18): 8387 - 8392. [Abstract] [Full Text] [PDF]

				S. Kinugawa, Z. Wang, P. M. Kaminski, M. S. Wolin, J. G. Edwards, G. Kaley, and T. H. Hintze Limited Exercise Capacity in Heterozygous Manganese Superoxide Dismutase Gene-Knockout Mice: Roles of Superoxide Anion and Nitric Oxide Circulation, March 29, 2005; 111(12): 1480 - 1486. [Abstract] [Full Text] [PDF]

				S. Papaiahgari, S. R. Kleeberger, H.-Y. Cho, D. V. Kalvakolanu, and S. P. Reddy NADPH Oxidase and ERK Signaling Regulates Hyperoxia-induced Nrf2-ARE Transcriptional Response in Pulmonary Epithelial Cells J. Biol. Chem., October 1, 2004; 279(40): 42302 - 42312. [Abstract] [Full Text] [PDF]

				J. J. Andresen, F. M. Faraci, and D. D. Heistad Vasomotor responses in MnSOD-deficient mice Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1141 - H1148. [Abstract] [Full Text] [PDF]

				K. S. Aulak, T. Koeck, J. W. Crabb, and D. J. Stuehr Dynamics of protein nitration in cells and mitochondria Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H30 - H38. [Abstract] [Full Text] [PDF]

				W. Li, T. Jue, J. Edwards, X. Wang, and T. H. Hintze Changes in NO bioavailabilty regulate cardiac O2 consumption: control by intramitochondrial SOD2 and intracellular myoglobin Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H47 - H54. [Abstract] [Full Text] [PDF]

				C.-L. M Cooke and S. T Davidge Endothelial-dependent vasodilation is reduced in mesenteric arteries from superoxide dismutase knockout mice Cardiovasc Res, December 1, 2003; 60(3): 635 - 642. [Abstract] [Full Text] [PDF]

				V. L. Kinnula and J. D. Crapo Superoxide Dismutases in the Lung and Human Lung Diseases Am. J. Respir. Crit. Care Med., June 15, 2003; 167(12): 1600 - 1619. [Abstract] [Full Text] [PDF]

				Y.-S. Ho Transgenic and Knockout Models for Studying the Role of Lung Antioxidant Enzymes in Defense against Hyperoxia Am. J. Respir. Crit. Care Med., December 15, 2002; 166(12): S51 - 56. [Abstract] [Full Text] [PDF]

				H.-Y. Cho, A. E. Jedlicka, S. P. M. Reddy, T. W. Kensler, M. Yamamoto, L.-Y. Zhang, and S. R. Kleeberger Role of NRF2 in Protection Against Hyperoxic Lung Injury in Mice Am. J. Respir. Cell Mol. Biol., February 1, 2002; 26(2): 175 - 182. [Abstract] [Full Text] [PDF]

				H. Kobayashi, R. Hataishi, H. Mitsufuji, M. Tanaka, M. Jacobson, T. Tomita, W. M. Zapol, and R. C. Jones Antiinflammatory Properties of Inducible Nitric Oxide Synthase in Acute Hyperoxic Lung Injury Am. J. Respir. Cell Mol. Biol., April 1, 2001; 24(4): 390 - 397. [Abstract] [Full Text]

				J.-C. COPIN, Y. GASCHE, Y. LI, and P. H. CHAN Prolonged hypoxia during cell development protects mature manganese superoxide dismutase-deficient astrocytes from damage by oxidative stress FASEB J, February 1, 2001; 15(2): 525 - 534. [Abstract] [Full Text] [PDF]

				M.-F. Tsan, X. Cao, J. E. White, J. Sacco, and C. Y. Lee Pertussis Toxin-Induced Lung Edema . Role of Manganese Superoxide Dismutase and Protein Kinase C Am. J. Respir. Cell Mol. Biol., March 1, 1999; 20(3): 465 - 473. [Abstract] [Full Text]