Figure 7
ET-1-induced PGE 2 release is mediated through a c-Src-dependent transactivation of EGFR/PI3K/Akt cascade. (A) Cells were incubated with 10 nM ET-1 for 6 h in the absence or presence of genistein (Gen, 10 nM), PP1 (100 nM), AG1478 (AG, 1 μM), LY294002 (LY, 00 nM), SH-5 (100 nM), U0126 (U0, 1 μM), SB202190 (SB, 300 nM), or SP600125 (SP, 300 nM), and the conditioned media were collected to assay the PGE2 level by EIA kit. Data are expressed as mean ± SEM of three individual experiments (n = 3). # P < 0.01, as compared with cells stimulated by ET-1 alone. (B) Schematic representation of signaling pathways involved in ET-1-induced COX-2 expression in bEnd.3 cells. Binding of ET-1 to Gi and Gq protein-coupled ETB receptors results in c-Src-dependent transactivation of EGFR/PI3K/Akt linking to MAPKs (e.g., ERK, p38 MAPK, and JNK) and c-Jun/AP-1. The COX-2 transcription is dependently regulated by MAPK-dependent AP-1 pathways. These signaling pathways contribute to sustained activation of AP-1 required for COX-2 expression and PGE2 release in bEnd.3 cells.