Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
|
pubmed:dateCreated |
1997-11-13
|
pubmed:abstractText |
Studies in vitro have shown that copper-zinc superoxide dismutase (CuZn-SOD) inhibits a number of events putatively involved in atherogenesis, including cell-mediated oxidation of LDL. To investigate whether increased activity of CuZn-SOD reduces atherogenesis in vivo, we examined diet-induced fatty streak formation in CuZn-SOD transgenic mice (n = 24) as compared with their nontransgenic littermates (n = 28). Transgenic animals were originally created by introduction of an EcoRI-BamHI human genomic DNA fragment containing the CuZn-SOD gene and its regulatory elements into B6SJL zygotes. For the current studies, the transgene was bred for 12 generations into the atherosclerosis-susceptible C57BL/6 background. Animals were fed atherogenic diets (15% fat, 1.25% cholesterol, 0.5% Na cholate) starting at 100 weeks of age and extending for 18 weeks. At the end of the diet period, aortic SOD activity was two-fold higher in transgenics than nontransgenics (mean +/- SE: 46.7 +/- 5.8 versus 20.1 +/- 2.4 units/mg of protein, P < .001). Levels of protein-bound amino acid oxidation products (meta-, ortho-, and dityrosine) were either similar or lower in aorta and heart from transgenics as compared with nontransgenics, suggesting that amplification of CuZn-SOD activity above the normal complement had modest inhibitory effects on basal oxidative stress in these tissues. CuZn-SOD overexpression did not reduce the extent of lesion development as analyzed by quantitative lipid staining of serial sections of the proximal aorta; mean lesion areas (+/- SE) were 997 +/- 478 and 943 +/- 221 mu 2 in transgenics and nontransgenics, respectively. Notably, the range of values for lesion area was 2.2-fold greater in transgenics (0-8403 versus 0-3868 mu 2 in nontransgenics). Moreover, within this group, lesion area showed a significant positive correlation with SOD activity (r = .611, P < .03). These results do not support an antiatherogenic effect of Cu-Zn-SOD over expression and raise the possibility that high tissue SOD activity may potentiate atherogenesis in fat-fed atherosclerosis-susceptible mice [corrected].
|
pubmed:grant | |
pubmed:commentsCorrections | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, HDL,
http://linkedlifedata.com/resource/pubmed/chemical/Dietary Fats,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase
|
pubmed:status |
MEDLINE
|
pubmed:month |
Sep
|
pubmed:issn |
1079-5642
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
17
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1734-40
|
pubmed:dateRevised |
2007-11-14
|
pubmed:meshHeading |
pubmed-meshheading:9327771-Amino Acids,
pubmed-meshheading:9327771-Animals,
pubmed-meshheading:9327771-Aorta,
pubmed-meshheading:9327771-Arteriosclerosis,
pubmed-meshheading:9327771-Cholesterol,
pubmed-meshheading:9327771-Cholesterol, HDL,
pubmed-meshheading:9327771-Dietary Fats,
pubmed-meshheading:9327771-Female,
pubmed-meshheading:9327771-Humans,
pubmed-meshheading:9327771-Lipoproteins,
pubmed-meshheading:9327771-Mice,
pubmed-meshheading:9327771-Mice, Inbred C57BL,
pubmed-meshheading:9327771-Mice, Transgenic,
pubmed-meshheading:9327771-Myocardium,
pubmed-meshheading:9327771-Oxidation-Reduction,
pubmed-meshheading:9327771-Superoxide Dismutase
|
pubmed:year |
1997
|
pubmed:articleTitle |
Fatty streak formation in fat-fed mice expressing human copper-zinc superoxide dismutase.
|
pubmed:affiliation |
Department of Molecular and Nuclear Medicine, Ernest Orlando Lawrence Berkeley National Laboratory, University of California, Berkeley 94720, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|