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

• Published in: Journal of inflammation research Vol. 5; no. default; pp. 51 - 58
• Main Authors: Charchaflieh, Jean, Labaze, Georges I, Li, Pulsar, Van Remmen, Holly, Lee, Haekyung, Stutz, Helen, Richardson, Arlan, Emanuel, Asher, Zhang, Ming
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2012; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: endotoxic shock; Genetic susceptibility; human SOD1 enzyme; Lipopolysaccharides; Observations; Properties; protective effect; Rodents; Septic shock; Short Report; Superoxide dismutase; transgenic mice; endotoxic shock; transgenic mice; protective effect; human SOD1 enzyme
• ISSN: 1178-7031; 1178-7031
• DOI: 10.2147/JIR.S32073

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. 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. 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). 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).