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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Guo, Hongtao Cai, Charles Q. Kuo, Paul C. |
| Abstract | The underlying redox-sensitive mechanisms that regulate hepatocyte expression of inducible nitric-oxide synthase (iNOS) and its antioxidant functions are largely unknown. We have demonstrated previously that oxidative stress induced by benzenetriol-mediated superoxide production increases interleukin-1β-induced iNOS protein synthesis, steady state iNOS mRNA expression, NO production, iNOS gene transcription, and trans-activation of the iNOS promoter in primary cultures of rat hepatocytes. In this study, we extend these studies by establishing the sequence specificity and binding of nuclear protein to the previously described 15-base cis-regulatory element of the rat hepatocyte iNOS promoter, isolating and identifying thecis-regulatory element transcription factor as hepatocyte nuclear factor-4α (HNF-4α), and confirming the functional role of HNF-4α in mediating redox-sensitive iNOS promoter trans-activation. In addition, we demonstrate that binding of HNF-4α to the transcriptional coactivator, PC4, in the presence of oxidative stress and interleukin-1β stimulation is essential for increased iNOS promoter activity in this setting. Our results indicate that HNF-4α is the transcription factor that mediates redox regulation of hepatocyte iNOS gene transcription. |
| Related Links | http://www.jbc.org/content/277/7/5054.abstract |
| Ending Page | 5060 |
| Starting Page | 5054 |
| Page Count | 7 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 7 |
| Volume Number | 277 |
| DOI | 10.1074/jbc.M109017200 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2002-02-15 |
| Access Restriction | Open |
| Subject Keyword | Inducible nitric-oxide synthase (iNOS) Benzenetriol (BZT) Interleukin (IL) Cis-regulatory element (ARE) Hepatocyte nuclear factor (HNF) Nucleotide(s) (nt) Dulbecco's phosphate-buffered saline (DPBS) Fetal calf serum (FCS) Phenylmethylsulfonyl fluoride (PMSF) Chloramphenicol acetyltransferase (CAT) Phosphate-buffered saline (PBS) MECHANISMS OF SIGNAL TRANSDUCTION |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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