Source:http://linkedlifedata.com/resource/pubmed/id/17942194
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4-5
|
| pubmed:dateCreated |
2008-2-1
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| pubmed:abstractText |
In the previous reports, we showed that the familial Alzheimer's disease (AD)-linked presenilin-1 (PS1) mutation induced the fragility to the endoplasmic reticulum (ER) stress and that caspase-4 mediates ER stress-induced- and beta-amyloid induced-apoptotic signaling in human cells. These results suggest the involvement of ER stress and caspase-4 in the cell death observed in AD. In this report, we studied the activation of caspase-4 in the familial AD-linked PS1 mutation (DeltaE9). Cleavage of caspase-4 under ER stress was enhanced by the overexpression of the familial AD-linked mutation (DeltaE9), showing that caspase-4 is a key caspase involved in the apoptotic signaling of AD. We also showed that the overexpression of caspase-4 induced cleavage of caspase-9 and caspase-3 without releasing cytochrome-c from the mitochondria. Thus, caspase-4 activates downstream caspases independently of mitochondrial apoptotic signaling and this might contribute to the pathogenesis of AD. To sum up our data, the familial AD-linked PS1 mutation accelerates the cleavage of caspase-4 under the ER stress and results in the activation of caspase-9 and caspase-3, apoptosis signal, without releasing cytochrome-c.
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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/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/CASP4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases, Initiator,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1
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| pubmed:status |
MEDLINE
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| pubmed:issn |
0197-0186
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
52
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
683-7
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:17942194-Actins,
pubmed-meshheading:17942194-Animals,
pubmed-meshheading:17942194-Apoptosis,
pubmed-meshheading:17942194-Blotting, Western,
pubmed-meshheading:17942194-COS Cells,
pubmed-meshheading:17942194-Caspase 3,
pubmed-meshheading:17942194-Caspase 9,
pubmed-meshheading:17942194-Caspases, Initiator,
pubmed-meshheading:17942194-Cells, Cultured,
pubmed-meshheading:17942194-Cercopithecus aethiops,
pubmed-meshheading:17942194-Cytochromes c,
pubmed-meshheading:17942194-Endoplasmic Reticulum,
pubmed-meshheading:17942194-Enzyme Activation,
pubmed-meshheading:17942194-Humans,
pubmed-meshheading:17942194-Mutation,
pubmed-meshheading:17942194-Presenilin-1,
pubmed-meshheading:17942194-Signal Transduction,
pubmed-meshheading:17942194-Stress, Physiological,
pubmed-meshheading:17942194-Subcellular Fractions
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| pubmed:articleTitle |
Presenilin-1 mutation activates the signaling pathway of caspase-4 in endoplasmic reticulum stress-induced apoptosis.
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| pubmed:affiliation |
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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