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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2002-3-21
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pubmed:abstractText |
While it has been reported that familial Alzheimer's disease (FAD)-linked mutants of amyloid precursor protein (APP) and presenilin (PS)2 induce neuronal cytotoxicity in a manner sensitive to antioxidant and pertussis toxin (PTX), little of the mechanism for PS1-mediated neuronal cell death has been characterized. We previously found that multiple mechanisms, different in detail, underlie cytotoxicities by two FAD-linked mutants of APP, using neuronal cells with an ecdysone-controlled expression system. Here we report that this system revealed that (i) low expression of FAD-linked M146L-PS1 caused neuronal cell death, whereas that of wild-type (wt)PS1 did not; (ii) mutation-specific cytotoxicity by M146L-PS1 was sensitive to antioxidant glutathione-ethyl-ester and resistant to Ac-DEVD-CHO; (iii) cytotoxicity by higher expression of wtPS1 was resistant to both; and (iv) cytotoxicity by M146L-PS1 was inhibited by PTX. It was also highly likely that the involved superoxide-generating enzyme was nitric oxide synthase (NOS), and that the PTX-sensitive cytotoxic signal by M146L-PS1 was mediated by none of the G(i/o) proteins. We conclude that M146L-PS1 activates a NOS-mediated cytotoxic pathway via a novel PTX target.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Protein Precursor,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Radiation-Protective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/S-ethyl glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella,
http://linkedlifedata.com/resource/pubmed/chemical/acetyl-aspartyl-glutamyl-valyl-aspar...,
http://linkedlifedata.com/resource/pubmed/chemical/omega-N-Methylarginine
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-3042
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
80
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
426-37
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11905990-Alzheimer Disease,
pubmed-meshheading:11905990-Amyloid beta-Protein Precursor,
pubmed-meshheading:11905990-Animals,
pubmed-meshheading:11905990-Cell Death,
pubmed-meshheading:11905990-Cysteine Proteinase Inhibitors,
pubmed-meshheading:11905990-Enzyme Inhibitors,
pubmed-meshheading:11905990-GTP-Binding Proteins,
pubmed-meshheading:11905990-Gene Expression,
pubmed-meshheading:11905990-Glutathione,
pubmed-meshheading:11905990-Membrane Proteins,
pubmed-meshheading:11905990-Mice,
pubmed-meshheading:11905990-NG-Nitroarginine Methyl Ester,
pubmed-meshheading:11905990-Neuroblastoma,
pubmed-meshheading:11905990-Neurons,
pubmed-meshheading:11905990-Neurotoxins,
pubmed-meshheading:11905990-Nitric Oxide Synthase,
pubmed-meshheading:11905990-Oligopeptides,
pubmed-meshheading:11905990-Pertussis Toxin,
pubmed-meshheading:11905990-Presenilin-1,
pubmed-meshheading:11905990-Radiation-Protective Agents,
pubmed-meshheading:11905990-Rats,
pubmed-meshheading:11905990-Tumor Cells, Cultured,
pubmed-meshheading:11905990-Virulence Factors, Bordetella,
pubmed-meshheading:11905990-omega-N-Methylarginine
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pubmed:year |
2002
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pubmed:articleTitle |
Neurotoxic mechanisms triggered by Alzheimer's disease-linked mutant M146L presenilin 1: involvement of NO synthase via a novel pertussis toxin target.
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pubmed:affiliation |
Department of Pharmacology and Neurosciences, KEIO University School of Medicine, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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