| First Author | Ptasinska A | Year | 2007 |
| Journal | FASEB J | Volume | 21 |
| Issue | 3 | Pages | 950-61 |
| PubMed ID | 17197391 | Mgi Jnum | J:119531 |
| Mgi Id | MGI:3702381 | Doi | 10.1096/fj.06-6822com |
| Citation | Ptasinska A, et al. (2007) Nitric oxide activation of peroxisome proliferator-activated receptor gamma through a p38 MAPK signaling pathway. FASEB J 21(3):950-61 |
| abstractText | Both nitric oxide (NO*) and peroxisome proliferator-activated receptors (PPARs) protect the endothelium and regulate its function. Here, we tested for crosstalk between these signaling pathways. Human umbilical vein and hybrid EA.hy926 endothelial cells were exposed to S-nitrosoglutathione (GSNO) or diethylenetriamine NONOate (DETA NONOate). Electrophoretic mobility shift assays using PPAR-response element (PPRE) probe showed that NO* caused a rapid dose-dependent increase in PPARgamma binding, an effect that was confirmed in vivo by chromatin immunoprecipitation. Conversely, N(G)-monomethyl-L-arginine, a NOS inhibitor, decreased PPARgamma binding. NO*-mediated PPARgamma binding and NO* induction of cyclooxygenase-2 (COX-2), diacylglycerol (DAG) kinase alpha (DGKalpha), and heme oxygenase-1 (HO-1), genes with well-characterized PPRE motifs, were cGMP independent. NO* dose dependently activated p38 MAPK, and p38 MAPK inhibition with SB202190 or knockdown with siRNA was shown to block NO* activation of PPARgamma. Likewise, p38 MAPK and PPARgamma inhibitors or knockdown of either transcript all significantly blocked NO* induction of PPRE-regulated genes. PPARgamma activation by p38 MAPK may contribute to the anti-inflammatory and cytoprotective effects of NO* in the vasculature. This crosstalk mechanism suggests new strategies for preventing and treating vascular dysfunction. |
