Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-8-22
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
226
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
98-104
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
NF-kappaB activation by triphenyltin triggers apoptosis in HL-60 cells.
pubmed:affiliation
Laboratory of Toxicology, Institute of Pharmacological Sciences, University of Milan, via Balzaretti 9, Milan, 20133, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't