Overexpression of human SOD1 improves survival of mice susceptible to endotoxic shock Journal Article

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Authors: Charchaflieh, J.; Labaze, G. I.; Li, P.; Van Remmen, H.; Lee, H.; Stutz, H.; Richardson, A.; Emanuel, A.; Zhang, M
Article Title: Overexpression of human SOD1 improves survival of mice susceptible to endotoxic shock
Abstract: BACKGROUND: Protective effects of the antioxidant enzyme Cu-Zn superoxide dismutase (SOD1) against endotoxic shock have not been demonstrated in animal models. We used a murine model to investigate whether overexpression of SOD1 protects against endotoxic shock, and whether the genetic background of SOD1 affects its effective protective effects and susceptibility to endotoxic shock. METHODS: Transgenic (tg) mice overexpressing human SOD1 and control mice were divided into four groups based on their genetic background: (1) tg mice with mixed genetic background (tg-JAX); (2) wild-type (WT) littermates of tg-JAX strain (WT-JAX); (3) tg mice with C57BL/6J background (tg-TX); (4) WT littermates of tg-TX strain (WT-TX). Activity of SOD1 in the intestine, heart, and liver of tg and control mice was confirmed using a polyacrylamide activity gel. Endotoxic shock was induced by intraperitoneal injection of lipopolysaccharide. Survival rates over 120 hours (mean, 95% confidence interval) were analyzed using Kaplan-Meier survival curves. RESULTS: Human SOD1 enzymatic activities were significantly higher in the intestine, heart, and liver of both tg strains (tg-JAX and tg-TX) compared with their WT littermates (WT-JAX and WT-TX, respectively). Interestingly, the endogenous SOD1 activities in tg-JAX mice were decreased compared with their WT littermates (WT-JAX), but such aberrant changes were not observed in tg-TX mice. There was no difference in the survival time between tg-JAX and WT-JAX groups after endotoxic shock (P > 0.05). However, the survival time in the tg-TX group was more than twofold longer than that in the WT-TX group (P 0.05). In addition, WT-JAX mice survived significantly longer than WT-TX mice (P 0.05). CONCLUSION: Aberrant decrease of endogenous SOD1 activities may have overshadowed the effect of overexpression of SOD1 in tg mice (tg-JAX). Mice with C57BL/6J background (tg-TX) are more susceptible to lipopolysaccharide-induced endotoxic shock than those with mixed genetic background (tg-JAX). Overexpression of SOD1 is protective only in mice with C57BL/6J background (tg-TX).
Journal Title: Journal of inflammation research
Volume: 5
ISSN: 1178-7031; 1178-7031
Publisher: Unknown  
Journal Place: New Zealand
Date Published: 2012
Start Page: 51
End Page: 58
Language: eng
DOI/URL:

10.2147/JIR.S32073
Notes: LR: 20130530; GR: R21 HL088527/HL/NHLBI NIH HHS/United States; JID: 101512684; OID: NLM: PMC3413208; OTO: NOTNLM; 2012/07/24 [epublish]; ppublish