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EP2 receptor activation by prostaglandin E2 leads to induction of HO-1 via PKA and PI3K pathways in C6 cells

2009; Elsevier BV; Volume: 379; Issue: 4 Linguagem: Inglês

10.1016/j.bbrc.2009.01.005

1090-2104

Min Kyu Park, Young Jin Kang, Yu Mi Ha, Jae Ju Jeong, Hye Jung Kim, Han Geuk Seo, Jae Heun Lee, Ki Churl Chang,

Nitric Oxide and Endothelin Effects

Recently we proposed that COX-2 induction precedes expression of HO-1 in ischemic preconditioned rat brain. In the current study, we investigated the molecular mechanism by which prostaglandin E2, one of COX-2 metabolites, induces HO-1 in rat C6 brain cells. We demonstrated that concentration of PGE2 increased HO-1 expression in C6 cells in vitro. The effects of PGE2 were mimicked by PGE2 receptor EP2 agonists, 11-deoxy PGE2, and cAMP analog, dibutyl-cAMP. HO-1 expression by PGE2 was inhibited by LY294002, PI3K inhibitor and H89, PKA inhibitor. The EP2-specific antagonist, AH8006 also inhibited PGE2-mediated HO-1 expression in a concentration-dependent manner. Finally, PGE2 inhibited GOX-induced apoptosis as assayed by FACS analysis or DNA strand breaks assay, and this cell death was reversed by ZnPPIX, HO-1 inhibitor. In addition to HO-1 induction, PGE2 also increased phosphorylation of Bad by PKA- and PI3K-depednent manner. Taken together, we conclude that PGE2 induces HO-1 protein expression through PKA and PI3K signaling pathways via EP2 receptor in C6 cells. The induction of HO-1 along with increase of p-Bad by PGE2 is responsible for anti-apoptosis against oxidant stress.