Loading...
Please wait, while we are loading the content...
An octamer motif is required for activation of the inducible nitric oxide synthase promoter in pancreatic beta-cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Darville, Martine I. Terryn, Sara Eizirik, Decio L. |
| Copyright Year | 2004 |
| Abstract | Nitric oxide, generated by the inducible form of nitric oxide synthase (iNOS), is a potential mediator of cytokine-induced beta-cell dysfunction in type 1 diabetes mellitus. We have previously shown that cytokine-induced iNOS expression is cycloheximide (CHX) sensitive and requires nuclear factor-kappa B (NF-kappa B) activation. In the present study, we show that an octamer motif located 20 bp downstream of the proximal NF-kappa B binding site in the rat iNOS promoter is critical for IL-1 beta and interferon-gamma induction of promoter activity in rat primary beta-cells and insulin-producing RINm5F cells. In gel shift assays, the octamer motif bound constitutively the transcription factor Oct1. Neither Oct1 nor NF-kappa B binding activities were blocked by CHX, suggesting that other factor(s) synthesized in response to IL-1 beta contribute to iNOS promoter induction. The high mobility group (HMG)-I(Y) protein also bound the proximal iNOS promoter region. HMG-I(Y) binding was decreased in cells treated with CHX and HMG-I(Y) silencing by RNA interference reduced IL-1 beta-induced iNOS promoter activity. These results suggest that Oct1, NF-kappa B, and HMG-I(Y) cooperate for transactivation of the iNOS promoter in pancreatic beta-cells. |
| Starting Page | 1 |
| Ending Page | 1 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://endo.endojournals.org/cgi/reprint/145/3/1130.pdf |
| PubMed reference number | 14630716v1 |
| Volume Number | 145 |
| Issue Number | 3 |
| Journal | Endocrinology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Cycloheximide Diabetes Mellitus Diabetes Mellitus, Insulin-Dependent HMGA1a Protein Interferon Type II Interleukin-1 beta Mediator brand of benfluorex hydrochloride NF-kappa B NOS2A protein, human Nitric Oxide Synthase Promoter Regions, Genetic Protein Domain RNA Interference TRANSCRIPTION FACTOR Trans-Activation, Genetic cytokine |
| Content Type | Text |
| Resource Type | Article |
