AI Article Synopsis
- The study aimed to determine if overexpressing the antioxidant enzyme SOD1 provides protection against endotoxic shock in mice and how genetic background influences this effect.
- Transgenic mice overexpressing human SOD1 were compared to control mice across different genetic backgrounds, and their survival rates after induced endotoxic shock were measured.
- Results showed that while overexpressed SOD1 activity was higher in both transgenic strains, only the tg-TX group exhibited significantly improved survival compared to their controls, whereas tg-JAX mice did not show any survival advantage likely due to reduced endogenous SOD1 activity.
Article 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).
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413208 | PMC |
| http://dx.doi.org/10.2147/JIR.S32073 | DOI Listing |
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