Source:http://linkedlifedata.com/resource/pubmed/id/11170175
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rdf:type | |
lifeskim:mentions |
umls-concept:C0109317,
umls-concept:C0127400,
umls-concept:C0162638,
umls-concept:C0752312,
umls-concept:C0815000,
umls-concept:C1150579,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1705767,
umls-concept:C1705791,
umls-concept:C1720655,
umls-concept:C1879547,
umls-concept:C1947974,
umls-concept:C2700455
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pubmed:issue |
3
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pubmed:dateCreated |
2001-2-22
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pubmed:abstractText |
Phosphorylated tau protein is the major component of paired helical filaments in Alzheimer disease (AD). We have previously shown that abnormal tau phosphorylation was induced in neuroblastoma SK-N-SH cells by the anticancer drug, paclitaxel, during apoptosis [Guise et al., 1999: Apoptosis 4:47-58]. In the present study, we first demonstrated a shift from fetal tau to hyperphosphorylated tau after incubation with paclitaxel, that showed some similarities with the hyperphosphorylated tau in AD, by using several tau antibodies, N-Term, Tau-1 and AT-8. Tau phosphorylation occurred independently of caspase-3 activation. We next showed that a sustained activation of ERK (extracellular signal-regulated kinase) induced both tau phosphorylation and apoptosis during paclitaxel treatment (1 microM). The inhibition of ERK activation by using the pharmacological MEK1/2 inhibitor, PD98059 (50 microM), or an antisense strategy, reduced tau phosphorylation and neuronal apoptosis (P < 0.001), indicating a link between ERK activation, tau phosphorylation and apoptosis. Doxorubicin (0.2 microM), an anticancer drug whose mechanism of action is independent of microtubules, also induced ERK activation, tau phosphorylation and apoptosis. Moreover, doxorubicin induced some morphological features of neurodegeneration such as loss of neurites and disorganization of the cytoskeleton in apoptotic neuroblastoma cells. Altogether, our results suggest that tau phosphorylation plays a significant role in apoptosis enhancing disruption of microtubules that in turn leads to formation of apoptotic bodies, suggesting that neurodegeneration and apoptosis are related.
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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/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Paclitaxel,
http://linkedlifedata.com/resource/pubmed/chemical/tau Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/tau-1 monoclonal antibody
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0360-4012
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2001 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
63
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
257-67
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pubmed:dateRevised |
2011-8-2
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pubmed:meshHeading |
pubmed-meshheading:11170175-Alzheimer Disease,
pubmed-meshheading:11170175-Antibodies, Monoclonal,
pubmed-meshheading:11170175-Antineoplastic Agents,
pubmed-meshheading:11170175-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:11170175-Apoptosis,
pubmed-meshheading:11170175-Caspases,
pubmed-meshheading:11170175-Doxorubicin,
pubmed-meshheading:11170175-Humans,
pubmed-meshheading:11170175-Microtubules,
pubmed-meshheading:11170175-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11170175-Nerve Degeneration,
pubmed-meshheading:11170175-Neuroblastoma,
pubmed-meshheading:11170175-Paclitaxel,
pubmed-meshheading:11170175-Phosphorylation,
pubmed-meshheading:11170175-Tumor Cells, Cultured,
pubmed-meshheading:11170175-tau Proteins
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pubmed:year |
2001
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pubmed:articleTitle |
Hyperphosphorylation of tau is mediated by ERK activation during anticancer drug-induced apoptosis in neuroblastoma cells.
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pubmed:affiliation |
UMR CNRS 6032, University of la Méditerranée, Faculty of Pharmacy, Marseille, France.
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pubmed:publicationType |
Journal Article
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