Multiple deficiencies in antioxidant enzymes in mice result in a compound increase in sensitivity to oxidative stress
| Autor: | Marian Sabia, Zhong Mao Guo, Ting-Ting Huang, Holly Van Remmen, Larry Estlack, Arlan Richardson, Charles J. Epstein, Wenbo Qi, Shuko Lee, Hong Yang, Gregory Freeman, Randy Strong |
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| Rok vydání: | 2004 |
| Předmět: |
Paraquat
GPX1 Antioxidant Time Factors Genotype medicine.medical_treatment SOD2 Myocardial Ischemia Mice Transgenic Biology medicine.disease_cause Biochemistry Antioxidants Superoxide dismutase chemistry.chemical_compound Mice Cytosol Physiology (medical) medicine Animals skin and connective tissue diseases Skin chemistry.chemical_classification Mice Knockout Glutathione Peroxidase Superoxide Dismutase Glutathione peroxidase Body Weight Fibroblasts medicine.disease Molecular biology Mitochondria Oxidative Stress chemistry Gamma Rays Reperfusion Injury cardiovascular system biology.protein Reperfusion injury Oxidative stress |
| Zdroj: | Free radical biologymedicine. 36(12) |
| ISSN: | 0891-5849 |
| Popis: | To examine the effect of compound deficiencies in antioxidant defense, we have generated mice (Sod2(+/-)/Gpx1(-/-)) that are deficient in Mn superoxide dismutase (MnSOD) and glutathione peroxidase 1 (Gpx1) by breeding Sod2(+/-) and Gpx1(-/-) mice together. Although Sod2(+/-)/Gpx1(-/-) mice showed a 50% reduction in MnSOD and no detectable Gpx1 activity in either mitochondria or cytosol in all tissues, they were viable and appeared normal. Fibroblasts isolated from Sod2(+/-)/Gpx1(-/-) mice were more sensitive (4- to 6-fold) to oxidative stress (t-butyl hydroperoxide or gamma irradiation) than fibroblasts from wild-type mice, and were twice as sensitive as cells from Sod2(+/-) or Gpx1(-/-) mice. Whole-animal studies demonstrated that survival of the Sod2(+/-)/Gpx1(-/-) mice in response to whole body gamma irradiation or paraquat administration was also reduced compared with that of wild-type, Sod2(+/-), or Gpx1(-/-) mice. Similarly, endogenous oxidative stress induced by cardiac ischemia/reperfusion injury led to greater apoptosis in heart tissue from the Sod2(+/-)/Gpx1(-/-) mice than in that from mice deficient in either MnSOD or Gpx1 alone. These data show that Sod2(+/-)/Gpx1(-/-) mice, deficient in two mitochondrial antioxidant enzymes, have significantly enhanced sensitivity to oxidative stress induced by exogenous insults and to endogenous oxidative stress compared with either wild-type mice or mice deficient in either MnSOD or Gpx1 alone. |
| Databáze: | OpenAIRE |
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