| First Author | Rao JS | Year | 2005 |
| Journal | Brain Res Mol Brain Res | Volume | 139 |
| Issue | 2 | Pages | 217-24 |
| PubMed ID | 16055227 | Mgi Jnum | J:102240 |
| Mgi Id | MGI:3607105 | Doi | 10.1016/j.molbrainres.2005.05.008 |
| Citation | Rao JS, et al. (2005) Down-regulation of brain nuclear factor-kappa B pathway in the cyclooxygenase-2 knockout mouse. Brain Res Mol Brain Res 139(2):217-24 |
| abstractText | Cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. Evidence suggests that neuronal COX-2 gene expression is mainly regulated by the transcription factor nuclear factor kappa-B (NF-kappaB). The present study was undertaken to determine whether there is a shared regulation of NF-kappaB or of nuclear factor of activated T-cells cytoplasmic (NFATc) with COX-2 and whether these transcription factors known to regulate COX-2 expression are altered in brain from COX-2 knockout (COX-2-/-) mice compared to wild type. We found a decrease in NF-kappaB DNA-protein binding activity, which was accompanied by a reduction of the phosphorylation state of both I-kappaBalpha and p65 proteins in the COX-2-/- mice. The mRNA and protein levels of p65 were also reduced in COX-2-/- mice, whereas total cytoplasmic I-kappaB protein level was not significantly changed. Taken together, these changes may be responsible for the observed decrease in NF-kappaB DNA binding activity. NF-kappaB DNA binding activity was selectively affected in the COX-2-/- mice compared to the wild type as there was no significant change in NFATc DNA binding activity. Overall, our data indicate that constitutive brain NF-kappaB activity is decreased in COX-2 deficient mice and suggest a reciprocal coupling between NF-kappaB and COX-2. |
