Linked Life Data

16044154

Source:http://linkedlifedata.com/resource/pubmed/id/16044154

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
2005-11-3
pubmed:abstractText
All-trans retinoic acid (ATRA) significantly improves the survival of patients with acute promyelocytic leukemia (APL) by inducing granulocytic differentiation of leukemia cells. Since an activation of the transcription factor NF-kappaB occurs during ATRA-induced maturation of APL cells, a mechanistic link between these two processes was investigated. Using an in vitro model for APL, we report that ectopic overexpression of a repressor of NF-kappaB activation did not affect granulocytic differentiation. Importantly, NF-kappaB inhibition markedly resulted in a decreased viability of the differentiated cells, which correlated with increased apoptosis. Apoptosis was accompanied by a sustained activation of the c-Jun N-terminal kinase (JNK). Inhibition of JNK by the specific inhibitor SP600125 or by transfection of a dominant-negative mutant of JNK1 reduced the percentage of apoptotic cells, thus showing that JNK activation constitutes a death signal. Furthermore, impairment of NF-kappaB activation resulted in increased levels of reactive oxygen species (ROS) upon ATRA treatment. ROS accumulation was suppressed by the antioxidant butylated hydroxyanisol, which also abolished ATRA-induced JNK activation and apoptosis. Altogether, our results demonstrate an anti-apoptotic effect of NF-kappaB activation during ATRA-induced differentiation of NB4 cells and identify repression of ROS-mediated JNK activation as a mechanism for this effect. Our observations also suggest that NF-kappaB signalling may contribute to an accumulation of mature APL cells and participate in the development of ATRA syndrome.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0950-9232
pubmed:author
pubmed:copyrightInfo
Oncogene (2005) 24, 7145-7155. doi:10.1038/sj.onc.1208889; published online 25 July 2005.
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7145-55
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16044154-Antigens, CD11c, pubmed-meshheading:16044154-Antioxidants, pubmed-meshheading:16044154-Apoptosis, pubmed-meshheading:16044154-Blotting, Western, pubmed-meshheading:16044154-Butylated Hydroxyanisole, pubmed-meshheading:16044154-Cell Aging, pubmed-meshheading:16044154-Cell Differentiation, pubmed-meshheading:16044154-Cell Line, Tumor, pubmed-meshheading:16044154-Cell Survival, pubmed-meshheading:16044154-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:16044154-Enzyme Activation, pubmed-meshheading:16044154-Flow Cytometry, pubmed-meshheading:16044154-Fluorescent Antibody Technique, Direct, pubmed-meshheading:16044154-Gene Expression Regulation, Leukemic, pubmed-meshheading:16044154-Granulocytes, pubmed-meshheading:16044154-Humans, pubmed-meshheading:16044154-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:16044154-Leukemia, Promyelocytic, Acute, pubmed-meshheading:16044154-NF-kappa B, pubmed-meshheading:16044154-Reactive Oxygen Species, pubmed-meshheading:16044154-Retroviridae, pubmed-meshheading:16044154-Spectrometry, X-Ray Emission, pubmed-meshheading:16044154-Tretinoin
pubmed:year
2005
pubmed:articleTitle
Retinoid-induced activation of NF-kappaB in APL cells is not essential for granulocytic differentiation, but prolongs the life span of mature cells.
pubmed:affiliation
INSERM U685, Centre Hayem, Hôpital St Louis, 1 avenue Claude Vellefaux, 75475 Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't