| pubmed-article:11069947 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11069947 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:11069947 | lifeskim:mentions | umls-concept:C0521390 | lld:lifeskim |
| pubmed-article:11069947 | lifeskim:mentions | umls-concept:C0018296 | lld:lifeskim |
| pubmed-article:11069947 | lifeskim:mentions | umls-concept:C0052201 | lld:lifeskim |
| pubmed-article:11069947 | lifeskim:mentions | umls-concept:C1416912 | lld:lifeskim |
| pubmed-article:11069947 | pubmed:issue | 22 | lld:pubmed |
| pubmed-article:11069947 | pubmed:dateCreated | 2000-11-14 | lld:pubmed |
| pubmed-article:11069947 | pubmed:abstractText | The epsilon4 genotype of apolipoprotein E (apoE4) is the most established predisposing factor in Alzheimer's disease (AD); however, it remains unclear how apoE4 contributes to the pathophysiology. Here, we report that the apoE4 protein (ApoE4) evokes apoptosis in neuronal cells through the low-density lipoprotein receptor-related protein (LRP) and heterotrimeric GTPases. We examined neuron/neuroblastoma hybrid F11 cells and found that these cells were killed by 30 microg/ml ApoE4, but not by 30 microg/ml ApoE3. ApoE4-induced death occurred with typical features for apoptosis in time- and dose-dependent manners, and was observed in SH-SY5Y neuroblastomas, but not in glioblastomas or non-neuronal Chinese hamster ovary cells. Activated, but not native, alpha2-macroglobulin suppressed this ApoE4 toxicity. Suppression by the antisense oligonucleotide to LRP and inhibition by low nanomolar concentrations of LRP-associated protein RAP provided evidence for the involvement of LRP. The involvement of heterotrimeric GTPases was demonstrated by the findings that (1) ApoE4-induced death was suppressed by pertussis toxin (PTX), but not by heat-inactivated PTX; and (2) transfection with PTX-resistant mutant cDNAs of Galpha(i) restored the toxicity of ApoE4 restricted by PTX. We thus conclude that one of the neurotoxic mechanisms triggered by ApoE4 is to activate a cell type-specific apoptogenic program involving LRP and the G(i) class of GTPases and that the apoE4 gene may play a direct role in the pathogenesis of AD and other forms of dementia. | lld:pubmed |
| pubmed-article:11069947 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11069947 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11069947 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11069947 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:11069947 | pubmed:issn | 1529-2401 | lld:pubmed |
| pubmed-article:11069947 | pubmed:author | pubmed-author:ItoYY | lld:pubmed |
| pubmed-article:11069947 | pubmed:author | pubmed-author:AbeYY | lld:pubmed |
| pubmed-article:11069947 | pubmed:author | pubmed-author:HashimotoYY | lld:pubmed |
| pubmed-article:11069947 | pubmed:author | pubmed-author:HagiwaraAA | lld:pubmed |
| pubmed-article:11069947 | pubmed:author | pubmed-author:MurayamaYY | lld:pubmed |
| pubmed-article:11069947 | pubmed:author | pubmed-author:UmezawaKK | lld:pubmed |
| pubmed-article:11069947 | pubmed:author | pubmed-author:JiangHH | lld:pubmed |
| pubmed-article:11069947 | pubmed:author | pubmed-author:NishimotoII | lld:pubmed |
| pubmed-article:11069947 | pubmed:author | pubmed-author:NiikuraTT | lld:pubmed |
| pubmed-article:11069947 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:11069947 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:11069947 | pubmed:volume | 20 | lld:pubmed |
| pubmed-article:11069947 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11069947 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11069947 | pubmed:pagination | 8401-9 | lld:pubmed |
| pubmed-article:11069947 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
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| pubmed-article:11069947 | pubmed:year | 2000 | lld:pubmed |
| pubmed-article:11069947 | pubmed:articleTitle | Neuronal apoptosis by apolipoprotein E4 through low-density lipoprotein receptor-related protein and heterotrimeric GTPases. | lld:pubmed |
| pubmed-article:11069947 | pubmed:affiliation | Department of Pharmacology and Neurosciences, KEIO University School of Medicine, Shinanomachi, Tokyo 160, Japan. | lld:pubmed |
| pubmed-article:11069947 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:11069947 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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