Linked Life Data

15657352

Source:http://linkedlifedata.com/resource/pubmed/id/15657352

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-1-19
pubmed:abstractText
Previously, alpha-tocopheryl succinate (alpha-TOS) has been reported to induce caspase-mediated apoptosis in PC-3 human prostate cancer cells. Caspase-9 was among several initiator caspases activated by alpha-TOS, suggesting a potential contribution of the intrinsic apoptotic pathway in mediating the response to alpha-TOS. Gene expression microarray was carried out as a screen to identify novel signaling molecules modulated by alpha-TOS, with a special focus on those known to play a role in mitochondria-mediated apoptosis. We discovered that Ask1, GADD45beta, and Sek1, three key components of the stress-activated mitogen-activated protein kinase pathway, are novel targets of alpha-TOS. Western blot analysis showed increased levels of phospho-Sek1 and phospho-c-Jun-NH2-kinase (JNK) in addition to total Ask1, GADD45beta, and Sek1. alpha-TOS also altered JNK-specific phosphorylation of Bcl-2 and Bim in a manner consistent with enhanced mitochondrial translocation of Bax and Bim. Because the expression level of most Bcl-2 family members remained unchanged, the posttranslational modification of Bcl-2 and Bim by JNK is likely to be a driving force in alpha-TOS activation of the intrinsic apoptotic pathway. Based on our findings, we propose a working model to capture the salient features of the apoptotic signaling circuitry of alpha-TOS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43-50
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Up-regulation of c-Jun-NH2-kinase pathway contributes to the induction of mitochondria-mediated apoptosis by alpha-tocopheryl succinate in human prostate cancer cells.
pubmed:affiliation
Department of Cancer Chemoprevention, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.