Impact Of Copper, Zinc Superoxide Dismutase Knockout On Lipid Metabolism In Mice
| dc.contributor.author | Wang, Shikui | en_US |
| dc.date.accessioned | 2009-10-14T20:05:47Z | |
| dc.date.available | 2014-10-14T06:24:18Z | |
| dc.date.issued | 2009-10-14T20:05:47Z | |
| dc.description.abstract | Antioxidant enzymes play important roles in maintaining the cellular redox homeostasis and protecting cell from damage caused by reactive oxygen species (ROS). Copper,zinc superoxide dismutase (SOD1) is an important antioxidant enzyme responsible for the clearance of superoxide anion. It has been suggested that the deficiencies of superoxide dismutases lead to abnormal lipid deposition in different organs. However, the regulatory role of SOD1 in lipid metabolism is largely unknown. The objective of this study was to determine the role of SOD1 in lipid metabolism. The experiments were conducted on the young and adult SOD1 knockout (SOD1-/-) and WT mice fed high fat, copper deficient, copper excess, or normal diets. Under the normal conditions, the SOD1 knockout causes hypercholesterolemia and hypotriglyceridemia with irregular lipids accumulation in liver, heart, kidney, muscle and testis. In contrast to the suppressed accumulation of fatty acids/triglyceride, the cholesterol synthetic pathway was consistently activated in SOD1-/- mice as indicated by increased mRNA and protein levels of related genes. The significant increase of sterol regulatory element binding proteins (SREBP) 2 and decrease of SREBP1 in SOD1-/- mice were observed. SOD1-/- mice fed high fat diet had reduced body weight and very low density lipoproteins (V)LDL triglyceride, although the total plasma cholesterol, total triglyceride and fecal cholesterol was not significantly affected. Copper deficiency did not affect the concentrations of blood lipids in SOD1-/- mice while high copper was found only to reduce hepatic triglyceride level without effect on plasma cholesterol and triglyceride levels as well as hepatic cholesterol. Surprisingly, significant increase of total plasma cholesterol was observed in mice injected with herbicide diquat (DQ) in addition to the increased mRNA levels of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) and squalene epoxidase. HepG2 cells showed similar responses to diquat treatment with increased HMGCR mRNA level. In conclusion, knockout of SOD1 caused disorder in lipid metabolism associated with the increased transcription of genes involved in cholesterol synthesis. These changes were not reversed by the high fat diet or dietary copper supplementation and might be dependent on increased ROS level following loss of SOD1 function. | en_US |
| dc.identifier.other | bibid: 6714448 | |
| dc.identifier.uri | https://hdl.handle.net/1813/14048 | |
| dc.language.iso | en_US | en_US |
| dc.title | Impact Of Copper, Zinc Superoxide Dismutase Knockout On Lipid Metabolism In Mice | en_US |
| dc.type | dissertation or thesis | en_US |
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