دورية أكاديمية
Overexpression of human SOD1 improves survival of mice susceptible to endotoxic shock
العنوان: | Overexpression of human SOD1 improves survival of mice susceptible to endotoxic shock |
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المؤلفون: | Charchaflieh J, Labaze GI, Li P, Van Remmen H, Lee H, Stutz H, Richardson A, Emanuel A, Zhang M |
المصدر: | Journal of Inflammation Research, Vol 2012, Iss default, Pp 51-58 (2012) |
بيانات النشر: | Dove Medical Press, 2012. |
سنة النشر: | 2012 |
المجموعة: | LCC:Pathology LCC:Therapeutics. Pharmacology |
مصطلحات موضوعية: | Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950 |
الوصف: | Jean Charchaflieh,1,2 Georges I Labaze,1 Pulsar Li,1 Holly Van Remmen,3 Haekyung Lee,1 Helen Stutz,1 Arlan Richardson,3 Asher Emanuel,1 Ming Zhang1,41Department of Anesthesiology, State University of New York (SUNY) Downstate Medical Center, New York, NY, USA; 2Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA; 3Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; 4Department of Cell Biology, State University of New York (SUNY) Downstate Medical Center, New York, NY, USABackground: 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).Keywords: human SOD1 enzyme, endotoxic shock, transgenic mice, protective effect |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1178-7031 |
Relation: | http://www.dovepress.com/overexpression-of-human-sod1-improves-survival-of-mice-susceptible-to--a10492; https://doaj.org/toc/1178-7031 |
URL الوصول: | https://doaj.org/article/826c1338fbb7428eae40bf2fc053c95a |
رقم الأكسشن: | edsdoj.826c1338fbb7428eae40bf2fc053c95a |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 11787031 |
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