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ATP‐induced COX‐2 expression via p42/p44 MAPK, p38, and NF‐κB in vascular smooth muscle cells
Author(s) -
Wang WeiJung,
Yang ChuenMao
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a229-a
Subject(s) - wortmannin , ly294002 , vascular smooth muscle , p38 mitogen activated protein kinases , mapk/erk pathway , microbiology and biotechnology , protein kinase b , kinase , chemistry , nf κb , proto oncogene tyrosine protein kinase src , phosphorylation , signal transduction , biology , endocrinology , smooth muscle
ATP has been shown to induce the expression of cyclooxygenase‐2 (COX‐2) on vascular smooth muscle cells (VSMCs) and contributes to atherosclerosis. However, the mechanisms underlying ATP‐induced COX‐2 expression in rat VSMCs were not completely understood. Here, we demonstrated that ATP induced expression of COX‐2 protein and mRNA in a time‐ and concentration‐dependent manner, which was attenuated by inhibitors of tyrosine kinase (genistein), Src (PP1), PKC (GF109203X and GO6976), PI3‐K (LY294002 and wortmannin), MEK1/2 (U0126), p38 (SB202190), and NF‐κB (helenalin). Consistently, ATP‐stimulated phosphorylation of p42/p44 MAPK and Akt were attenuated by U0126 and LY294002, respectively. These results suggest that in VSMCs, activation of p42/p44 MAPK, p38, and NF‐κB pathways are essential for ATP‐induced COX‐2 gene expression. These results provide new insight into the mechanisms of ATP action that nucleotides may promote atherosclerosis in the cardiovascular disease.