Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2003-4-8
pubmed:abstractText
Using a cDNA microarray analysis, we identified x-ray-inducible immediate early response factor-1 (IEX-1) as a proapoptotic gene which was induced by TNF-alpha and also depend on NF-kappaB activation in Hc human hepatocytes. In these cells only the original form of IEX-1, termed IEX-1S, but not its longer transcript IEX-1L, was expressed. Overexpression of IEX-1S resulted in promotion of TNF-alpha-induced apoptosis in Hc cells expressing a mutant form of IkappaB. This proapoptotic action can be explained by its inhibitory findings on survival signals; inhibition of TNF-alpha-induced activation and expression of phosphatidylinositol 3-kinase (PI3K)/Akt, and also blockage of expression of Mcl-1, an antiapoptotic Bcl-2 family member which is located downstream of Akt, was inhibited by IEX-1S. LY 294002, an inhibitor of PI3K, increased IEX-1S expression induced by TNF-alpha and accelerated TNF-alpha-induced apoptosis in IkappaB-treated Hc cells. Overexpression of the dominant-negative Akt enhanced, but the constitutively active Akt suppressed, TNF-alpha-induced IEX-1S expression, suggesting that PI3K/Akt negatively regulated IEX-1S expression. These results demonstrate that NF-kappaB-dependent recruitment of IEX-1S may play a proapoptotic role in TNF-alpha-stimulated hepatocytes through blockage of the PI3K/Akt pathway. Moreover, the reciprocal cross-talk between IEX-1S and PI3K/Akt may closely be involved in the regulation of TNF-alpha-induced hepatocyte apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic, http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins, http://linkedlifedata.com/resource/pubmed/chemical/IER3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
170
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4053-60
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12682234-Adjuvants, Immunologic, pubmed-meshheading:12682234-Apoptosis, pubmed-meshheading:12682234-Apoptosis Regulatory Proteins, pubmed-meshheading:12682234-Cell Survival, pubmed-meshheading:12682234-Cells, Cultured, pubmed-meshheading:12682234-Enzyme Activation, pubmed-meshheading:12682234-Gene Expression Profiling, pubmed-meshheading:12682234-Gene Expression Regulation, pubmed-meshheading:12682234-Gene Targeting, pubmed-meshheading:12682234-Hepatocytes, pubmed-meshheading:12682234-Humans, pubmed-meshheading:12682234-Immediate-Early Proteins, pubmed-meshheading:12682234-Membrane Proteins, pubmed-meshheading:12682234-Multigene Family, pubmed-meshheading:12682234-NF-kappa B, pubmed-meshheading:12682234-Neoplasm Proteins, pubmed-meshheading:12682234-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:12682234-Phosphatidylinositol 3-Kinases, pubmed-meshheading:12682234-Protein-Serine-Threonine Kinases, pubmed-meshheading:12682234-Proto-Oncogene Proteins, pubmed-meshheading:12682234-Proto-Oncogene Proteins c-akt, pubmed-meshheading:12682234-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:12682234-Signal Transduction, pubmed-meshheading:12682234-Transfection, pubmed-meshheading:12682234-Tumor Necrosis Factor-alpha, pubmed-meshheading:12682234-X-Rays
pubmed:year
2003
pubmed:articleTitle
Expression of the NF-kappa B target gene X-ray-inducible immediate early response factor-1 short enhances TNF-alpha-induced hepatocyte apoptosis by inhibiting Akt activation.
pubmed:affiliation
First Department of Internal Medicine, Gifu University School of Medicine, Tsukasamachi, Gifu, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't