PMID- 12682234
OWN - NLM
STAT- MEDLINE
DCOM- 20030731
LR  - 20211203
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 170
IP  - 8
DP  - 2003 Apr 15
TI  - 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.
PG  - 4053-60
AB  - 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.
FAU - Osawa, Yosuke
AU  - Osawa Y
AD  - First Department of Internal Medicine, Gifu University School of Medicine, 
      Tsukasamachi, Gifu, Japan.
FAU - Nagaki, Masahito
AU  - Nagaki M
FAU - Banno, Yoshiko
AU  - Banno Y
FAU - Brenner, David A
AU  - Brenner DA
FAU - Nozawa, Yoshinori
AU  - Nozawa Y
FAU - Moriwaki, Hisataka
AU  - Moriwaki H
FAU - Nakashima, Shigeru
AU  - Nakashima S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (IER3 protein, human)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Adjuvants, Immunologic/biosynthesis/*genetics/physiology/radiation effects
MH  - Apoptosis/*genetics/physiology
MH  - Apoptosis Regulatory Proteins
MH  - Cell Survival/physiology
MH  - Cells, Cultured
MH  - Enzyme Activation/genetics
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation/radiation effects
MH  - Gene Targeting/*methods
MH  - Hepatocytes/cytology/enzymology/*metabolism
MH  - Humans
MH  - Immediate-Early Proteins/biosynthesis/*genetics/physiology/radiation effects
MH  - Membrane Proteins
MH  - Multigene Family
MH  - NF-kappa B/*metabolism/physiology
MH  - Neoplasm Proteins/biosynthesis/*genetics/physiology/radiation effects
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/*antagonists & inhibitors/metabolism/physiology
MH  - Proto-Oncogene Proteins c-akt
MH  - Proto-Oncogene Proteins c-bcl-2/biosynthesis/genetics
MH  - Signal Transduction/genetics
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - X-Rays
EDAT- 2003/04/19 05:00
MHDA- 2003/08/02 05:00
CRDT- 2003/04/19 05:00
PHST- 2003/04/19 05:00 [pubmed]
PHST- 2003/08/02 05:00 [medline]
PHST- 2003/04/19 05:00 [entrez]
AID - 10.4049/jimmunol.170.8.4053 [doi]
PST - ppublish
SO  - J Immunol. 2003 Apr 15;170(8):4053-60. doi: 10.4049/jimmunol.170.8.4053.