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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1996-8-22
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pubmed:abstractText |
Trisubstituted organotin pesticides are lethal for different cell types. In this study we investigated whether triphenyltin chloride (TPT) causes apoptosis in HL-60 promyelocytic cells and, if so, by what mechanisms. We report that 5 microM TPT increased intracellular Ca2+ in HL-60 cells within seconds; concomitantly actin depolymerization was detected 30 s and 1 min after the treatment. This was followed 15 min later by NF-kappaB activation, and apoptotic bodies and DNA fragmentation were evident after 3 and 6 h, respectively. At these times TPT also induced the release of tumor necrosis factor-alpha (TNF-alpha). Prior treatment of the cells with a polyclonal antibody to human TNF-alpha abolished TPT-induced DNA fragmentation, which suggests that the ultimate effect of TPT may be mediated by TNF-alpha. Prior treatment of the cells with 100 microM pyrrolidine dithiocarbamate, an antioxidant and potent inhibitor of NF-kappaB activation, prevented actin depolymerization, NF-kappaB activation, and DNA fragmentation, although it did not affect TPT-induced Ca2+ mobilization. These findings suggest that TPT increases intracellular Ca2+, alters actin polymerization and the cytoskeleton, and induces NF-kappaB activation, TNF-alpha synthesis, DNA degradation, and apoptosis. Reactive oxygen species seem to be essential to NF-kappaB activation, TNF-alpha synthesis, and the subsequent steps.
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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/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Organotin Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Polymers,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidines,
http://linkedlifedata.com/resource/pubmed/chemical/Thiocarbamates,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/pyrrolidine dithiocarbamic acid,
http://linkedlifedata.com/resource/pubmed/chemical/triphenyltin
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0014-4827
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
226
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
98-104
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8660944-Actins,
pubmed-meshheading:8660944-Antioxidants,
pubmed-meshheading:8660944-Apoptosis,
pubmed-meshheading:8660944-Base Sequence,
pubmed-meshheading:8660944-Calcium,
pubmed-meshheading:8660944-Cell Nucleus,
pubmed-meshheading:8660944-Cytoskeleton,
pubmed-meshheading:8660944-DNA,
pubmed-meshheading:8660944-DNA Damage,
pubmed-meshheading:8660944-HL-60 Cells,
pubmed-meshheading:8660944-Humans,
pubmed-meshheading:8660944-Molecular Sequence Data,
pubmed-meshheading:8660944-NF-kappa B,
pubmed-meshheading:8660944-Organotin Compounds,
pubmed-meshheading:8660944-Polymers,
pubmed-meshheading:8660944-Pyrrolidines,
pubmed-meshheading:8660944-Thiocarbamates,
pubmed-meshheading:8660944-Tumor Necrosis Factor-alpha
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pubmed:year |
1996
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pubmed:articleTitle |
NF-kappaB activation by triphenyltin triggers apoptosis in HL-60 cells.
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pubmed:affiliation |
Laboratory of Toxicology, Institute of Pharmacological Sciences, University of Milan, via Balzaretti 9, Milan, 20133, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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