Source:http://linkedlifedata.com/resource/pubmed/id/19679659
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
48
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| pubmed:dateCreated |
2009-11-25
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| pubmed:abstractText |
Increased oxidative damage is a prominent and early feature in Alzheimer disease. We previously crossed Alzheimer disease transgenic (APPsw) model mice with alpha-tocopherol transfer protein knock-out (Ttpa(-/-)) mice in which lipid peroxidation in the brain was significantly increased. The resulting double-mutant (Ttpa(-/-)APPsw) mice showed increased amyloid beta (Abeta) deposits in the brain, which was ameliorated with alpha-tocopherol supplementation. To investigate the mechanism of the increased Abeta accumulation, we here studied generation, degradation, aggregation, and efflux of Abeta in the mice. The clearance of intracerebral-microinjected (125)I-Abeta(1-40) from brain was decreased in Ttpa(-/-) mice to be compared with wild-type mice, whereas the generation of Abeta was not increased in Ttpa(-/-)APPsw mice. The activity of an Abeta-degrading enzyme, neprilysin, did not decrease, but the expression level of insulin-degrading enzyme was markedly decreased in Ttpa(-/-) mouse brain. In contrast, Abeta aggregation was accelerated in Ttpa(-/-) mouse brains compared with wild-type brains, and well known molecules involved in Abeta transport from brain to blood, low density lipoprotein receptor-related protein-1 (LRP-1) and p-glycoprotein, were up-regulated in the small vascular fraction of Ttpa(-/-) mouse brains. Moreover, the disappearance of intravenously administered (125)I-Abeta(1-40) was decreased in Ttpa(-/-) mice with reduced translocation of LRP-1 in the hepatocytes. These results suggest that lipid peroxidation due to depletion of alpha-tocopherol impairs Abeta clearances from the brain and from the blood, possibly causing increased Abeta accumulation in Ttpa(-/-)APPsw mouse brain and plasma.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid Precursor Protein Secretases,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tocopherols,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Tocopherol,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-tocopherol transfer protein
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
|
| pubmed:issn |
1083-351X
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| pubmed:author |
pubmed-author:ItoShingoS,
pubmed-author:IwataNobuhisaN,
pubmed-author:JishageKou-IchiK,
pubmed-author:MizusawaHidehiroH,
pubmed-author:NishidaYoichiroY,
pubmed-author:OhtsukiSumioS,
pubmed-author:PiaoWenyingW,
pubmed-author:SaidoTakaomi CTC,
pubmed-author:SasaguriHirokiH,
pubmed-author:TakahashiTsuburaT,
pubmed-author:TerasakiTetsuyaT,
pubmed-author:TomimitsuHiroyukiH,
pubmed-author:YamadaHiromiH,
pubmed-author:YamamotoNaokiN,
pubmed-author:YanagisawaKatsuhikoK,
pubmed-author:YokotaShigefumiS,
pubmed-author:YokotaTakanoriT
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| pubmed:issnType |
Electronic
|
| pubmed:day |
27
|
| pubmed:volume |
284
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
33400-8
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| pubmed:dateRevised |
2011-3-3
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| pubmed:meshHeading |
pubmed-meshheading:19679659-Alzheimer Disease,
pubmed-meshheading:19679659-Amyloid Precursor Protein Secretases,
pubmed-meshheading:19679659-Amyloid beta-Peptides,
pubmed-meshheading:19679659-Animals,
pubmed-meshheading:19679659-Blood-Brain Barrier,
pubmed-meshheading:19679659-Blotting, Northern,
pubmed-meshheading:19679659-Blotting, Western,
pubmed-meshheading:19679659-Brain,
pubmed-meshheading:19679659-Carrier Proteins,
pubmed-meshheading:19679659-Dietary Supplements,
pubmed-meshheading:19679659-Disease Models, Animal,
pubmed-meshheading:19679659-Female,
pubmed-meshheading:19679659-Humans,
pubmed-meshheading:19679659-Male,
pubmed-meshheading:19679659-Mice,
pubmed-meshheading:19679659-Mice, Inbred C57BL,
pubmed-meshheading:19679659-Mice, Knockout,
pubmed-meshheading:19679659-Mice, Transgenic,
pubmed-meshheading:19679659-Tocopherols,
pubmed-meshheading:19679659-alpha-Tocopherol
|
| pubmed:year |
2009
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| pubmed:articleTitle |
Depletion of vitamin E increases amyloid beta accumulation by decreasing its clearances from brain and blood in a mouse model of Alzheimer disease.
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| pubmed:affiliation |
Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519. Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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