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Redox-mediated upregulation of hepatocyte iNOS transcription requires coactivator PC4.

Publication ,  Journal Article
Marroquin, CE; Wai, PY; Kuo, PC; Guo, H
Published in: Surgery
July 2005

BACKGROUND: Redox-mediated upregulation of transcription of hepatocyte inducible nitric oxide synthase (iNOS) requires hepatocyte nuclear factor IV-alpha (HNF-4alpha). In this setting, PC4 is often isolated with HNF-4alpha in DNA-protein pull-down studies. Transcriptional coactivator PC4 facilitates activator-dependent transcription via interactions with basal transcriptional machinery that are independent of PC4-DNA binding. We hypothesized that PC4 is a necessary component of HNF-4alpha-regulated redox-sensitive hepatocyte iNOS transcription. METHODS: Murine CCL9.1 hepatocytes were stimulated with interleukin-1beta (IL-1beta; 1000 U/mL) in the presence and absence of peroxide (H(2)O(2); 50 nmol/L). Antisense and sense oligonucleotides to HNF-4alpha and PC4 were added selectively. Coimmunoprecipitation (Co-IP) studies determined the association between HNF-4alpha and PC4. Transient transfection was performed with the use of a luciferase reporter construct containing the murine iNOS promoter (1.8 kb). Chromatin immunoprecipitation assays determined in vivo binding of PC4 and HNF-4alpha to the iNOS promoter region. RESULTS: Ablation of either HNF-4alpha or PC4 blunted the peroxide-mediated increase in the activation of the iNOS promoter. In IL-1beta+H(2)O(2) only, co-IP studies demonstrated the presence of an HNF-4alpha-PC4 protein complex, and chromatin immunoprecipitation assays demonstrated that this complex binds to the genomic iNOS promoter. CONCLUSIONS: Redox-mediated upregulation of hepatocyte iNOS transcription requires an HNF-4alpha-PC4 transcriptional complex.

Duke Scholars

Published In

Surgery

DOI

ISSN

0039-6060

Publication Date

July 2005

Volume

138

Issue

1

Start / End Page

93 / 99

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transfection
  • Transcription, Genetic
  • Transcription Factors
  • Trans-Activators
  • Surgery
  • Repressor Proteins
  • Phosphoproteins
  • Oxidation-Reduction
  • Nitric Oxide Synthase Type II
 

Citation

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Marroquin, C. E., Wai, P. Y., Kuo, P. C., & Guo, H. (2005). Redox-mediated upregulation of hepatocyte iNOS transcription requires coactivator PC4. Surgery, 138(1), 93–99. https://doi.org/10.1016/j.surg.2005.03.014
Marroquin, Carlos E., Philip Y. Wai, Paul C. Kuo, and Hongtao Guo. “Redox-mediated upregulation of hepatocyte iNOS transcription requires coactivator PC4.Surgery 138, no. 1 (July 2005): 93–99. https://doi.org/10.1016/j.surg.2005.03.014.
Marroquin CE, Wai PY, Kuo PC, Guo H. Redox-mediated upregulation of hepatocyte iNOS transcription requires coactivator PC4. Surgery. 2005 Jul;138(1):93–9.
Marroquin, Carlos E., et al. “Redox-mediated upregulation of hepatocyte iNOS transcription requires coactivator PC4.Surgery, vol. 138, no. 1, July 2005, pp. 93–99. Pubmed, doi:10.1016/j.surg.2005.03.014.
Marroquin CE, Wai PY, Kuo PC, Guo H. Redox-mediated upregulation of hepatocyte iNOS transcription requires coactivator PC4. Surgery. 2005 Jul;138(1):93–99.
Journal cover image

Published In

Surgery

DOI

ISSN

0039-6060

Publication Date

July 2005

Volume

138

Issue

1

Start / End Page

93 / 99

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transfection
  • Transcription, Genetic
  • Transcription Factors
  • Trans-Activators
  • Surgery
  • Repressor Proteins
  • Phosphoproteins
  • Oxidation-Reduction
  • Nitric Oxide Synthase Type II