Source:http://linkedlifedata.com/resource/pubmed/id/15353207
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-2
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| pubmed:dateCreated |
2004-9-8
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| pubmed:abstractText |
Peroxisomes are ubiquitous subcellular organelles and abnormality in their biogenesis and specific gene defects leads to fatal demyelinating disorders. We report that neuroinflammatory disease in brain of experimental autoimmune encephalomyelitis (EAE) rats decreased the peroxisomal functions. Degradation of very long chain fatty acids decreased by 47% and resulted in its accumulation (C26:0, 40%). Decreased activity (66% of control) of dihydroxyacetonephosphate acyltransferase (DHAP-AT), first enzyme in plasmalogens biosynthesis, resulted in decreased levels of plasmalogens (16-30%). Catalase activity, a peroxisomal enzyme, was also reduced (37%). Gene microarray analysis of EAE spinal cord showed significant decrease in transcripts encoding peroxisomal proteins including catalase (folds 3.2; p<0.001) and DHAP-AT (folds 2.6; p<0.001). These changes were confirmed by quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, suggesting that decrease of peroxisomal functions in the central nervous system will have negative consequences for myelin integrity and repair because these lipids are major constituents of myelin. However, lovastatin (a cholesterol lowering and anti-inflammatory drug) administered during EAE induction provided protection against loss/down-regulation of peroxisomal functions. Attenuation of induction of neuroinflammatory mediators by statins in cultured brain cells [J. Clin. Invest. 100 (1997) 2671-2679], and in central nervous system of EAE animals and thus the EAE disease [J. Neurosci. Res. 66 (2001) 155-162] and the studies described here indicate that inflammatory mediators have a marked negative effect on peroxisomal functions and thus on myelin assembly and that these effects can be prevented by treatment with statins. These observations are of importance because statins are presently being tested as therapeutic agents against a number of neuroinflammatory demyelinating diseases.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Abcd3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Acyl-CoA Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Acyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Anticholesteremic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Catalase,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Freund's Adjuvant,
http://linkedlifedata.com/resource/pubmed/chemical/Lovastatin,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Pex6 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/glycerone-phosphate...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0006-8993
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
1022
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1-11
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15353207-ATP-Binding Cassette Transporters,
pubmed-meshheading:15353207-Acyl-CoA Oxidase,
pubmed-meshheading:15353207-Acyltransferases,
pubmed-meshheading:15353207-Adenosine Triphosphatases,
pubmed-meshheading:15353207-Animals,
pubmed-meshheading:15353207-Anticholesteremic Agents,
pubmed-meshheading:15353207-Catalase,
pubmed-meshheading:15353207-Central Nervous System,
pubmed-meshheading:15353207-Disease Models, Animal,
pubmed-meshheading:15353207-Encephalomyelitis, Autoimmune, Experimental,
pubmed-meshheading:15353207-Fatty Acids,
pubmed-meshheading:15353207-Female,
pubmed-meshheading:15353207-Freund's Adjuvant,
pubmed-meshheading:15353207-Immunohistochemistry,
pubmed-meshheading:15353207-Inflammation,
pubmed-meshheading:15353207-Lovastatin,
pubmed-meshheading:15353207-Membrane Proteins,
pubmed-meshheading:15353207-Microarray Analysis,
pubmed-meshheading:15353207-Peroxisomal Disorders,
pubmed-meshheading:15353207-Peroxisomes,
pubmed-meshheading:15353207-RNA, Messenger,
pubmed-meshheading:15353207-Rats,
pubmed-meshheading:15353207-Rats, Inbred Lew,
pubmed-meshheading:15353207-Reverse Transcriptase Polymerase Chain Reaction
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| pubmed:year |
2004
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| pubmed:articleTitle |
Impaired peroxisomal function in the central nervous system with inflammatory disease of experimental autoimmune encephalomyelitis animals and protection by lovastatin treatment.
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| pubmed:affiliation |
Department of Pediatrics, Medical University of South Carolina, 171 Ashley Avenue, Charleston SC 29425, USA. singhi@musc.edu
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, N.I.H., Extramural
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