PMID- 19438714
OWN - NLM
STAT- MEDLINE
DCOM- 20090717
LR  - 20161125
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 276
IP  - 12
DP  - 2009 Jun
TI  - The IkappaBalpha gene is a peroxisome proliferator-activated receptor cardiac 
      target gene.
PG  - 3247-55
LID - 10.1111/j.1742-4658.2009.07039.x [doi]
AB  - The purpose of this study was to provide a better understanding of the regulatory 
      role of the nuclear steroid receptor on the nuclear factor of kappa light 
      polypeptide gene enhancer in B cells (NFkappaB) in mouse heart. NFkappaB 
      regulates many nuclear genes and has been associated with many human cardiac 
      diseases. NFkappaB's protein regulator gene, nuclear factor of kappa light 
      polypeptide gene enhancer in B cells inhibitor alpha gene (IkappaBalpha), was 
      found in this study to be regulated by peroxisome proliferator-activated 
      receptors (PPARs). PPARs, retinoid X receptors (RXRs) and thyroid hormone 
      receptors (THRs) are members of the nuclear receptor superfamily, which consists 
      of a large number of transcription factors whose activities are regulated by 
      their cognate ligands. These steroid hormone receptors are important regulators 
      of gene expression and differentiation in the heart. These receptors form 
      homo-(RXR, THR) and hetero-(PPAR-RXR, RXR-THR) dimers that bind DNA at various 
      response elements (PPAR, RXR and THR) in the promoter regions of target genes. 
      The PPAR/RXR response elements in the promoter of IkappaBalpha are described in 
      this article. A known PPAR activator (Wy14643) and dimethylsulfoxide (vehicle) 
      were introduced into control (FVB) and delta337T thyroid hormone receptor 
      (TRbeta) transgenic mice. The delta337T TRbeta transgenic mouse has a resistance 
      to the thyroid hormone (RTH) phenotype. Affymetrix 430_2 chip gene expression was 
      examined for four study groups (control, control with Wy14643, delta337T TRbeta 
      and delta337T TRbeta with Wy14643), consisting of seven mice each. IkappaBalpha 
      mRNA expression in the Wy14643 control and in transgenic mice was upregulated 
      significantly in microarray (P < 0.05) and quantitative RT-PCR (P < 0.01) 
      analyses. The increase in mRNA level was also accompanied by an increase in 
      IkappaBalpha protein in cells, as measured by Western blot analysis. Duplex 
      oligo-DNAs containing the putative PPAR/RXR motif (AGGTCA/TCCAGT) from the 
      IkappaBalpha promoter were used in gel shift assays to verify the binding of PPAR 
      and RXR to their response elements. pGL4.0 [Luc] constructs of the IkappaBalpha 
      promoter, with and without the PPAR/RXR motifs, were co-transfected with mouse 
      PPAR alpha, beta and gamma(1) into HepG2 cells and used in luciferase assays to 
      verify gene activation. In conclusion, our study revealed that PPAR regulates the 
      mouse cardiac IkappaBalpha gene in both control and transgenic mouse heart. The 
      implications of this finding are discussed in relation to possible changes in 
      cardiac function.
FAU - Buroker, Norman E
AU  - Buroker NE
AD  - Department of Cardiology, Seattle Children's Hospital, WA 98195, USA. 
      nburoker@u.washington.edu
FAU - Barboza, Julia
AU  - Barboza J
FAU - Huang, Jie-Yu
AU  - Huang JY
LA  - eng
PT  - Journal Article
DEP - 20090429
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 0 (Peroxisome Proliferators)
RN  - 0 (Pyrimidines)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 86C4MRT55A (pirinixic acid)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Electrophoretic Mobility Shift Assay
MH  - Gene Expression/drug effects
MH  - Humans
MH  - I-kappa B Proteins/genetics/*metabolism
MH  - Luciferases/genetics/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Myocardium/*metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - Peroxisome Proliferator-Activated Receptors/genetics/*metabolism
MH  - Peroxisome Proliferators/pharmacology
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - Pyrimidines/administration & dosage/pharmacology
MH  - Receptors, Thyroid Hormone/genetics/*metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Retinoid X Receptors/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transfection
EDAT- 2009/05/15 09:00
MHDA- 2009/07/18 09:00
CRDT- 2009/05/15 09:00
PHST- 2009/05/15 09:00 [entrez]
PHST- 2009/05/15 09:00 [pubmed]
PHST- 2009/07/18 09:00 [medline]
AID - EJB7039 [pii]
AID - 10.1111/j.1742-4658.2009.07039.x [doi]
PST - ppublish
SO  - FEBS J. 2009 Jun;276(12):3247-55. doi: 10.1111/j.1742-4658.2009.07039.x. Epub 
      2009 Apr 29.