EP2 receptor activation by prostaglandin E2 leads to induction of HO-1 via PKA and PI3K pathways in C6 cells.
Biochem Biophys Res Commun
; 379(4): 1043-7, 2009 Feb 20.
Article
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| MEDLINE
| ID: mdl-19138674
ABSTRACT
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 E(2), one of COX-2 metabolites, induces HO-1 in rat C6 brain cells. We demonstrated that concentration of PGE(2) increased HO-1 expression in C6 cells in vitro. The effects of PGE(2) were mimicked by PGE(2) receptor EP(2) agonists, 11-deoxy PGE(2), and cAMP analog, dibutyl-cAMP. HO-1 expression by PGE(2) was inhibited by LY294002, PI3K inhibitor and H89, PKA inhibitor. The EP(2)-specific antagonist, AH8006 also inhibited PGE(2)-mediated HO-1 expression in a concentration-dependent manner. Finally, PGE(2) 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, PGE(2) also increased phosphorylation of Bad by PKA- and PI3K-depednent manner. Taken together, we conclude that PGE(2) induces HO-1 protein expression through PKA and PI3K signaling pathways via EP(2) receptor in C6 cells. The induction of HO-1 along with increase of p-Bad by PGE(2) is responsible for anti-apoptosis against oxidant stress.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Dinoprostona
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Apoptosis
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Receptores de Prostaglandina E
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Hemo-Oxigenasa 1
Límite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2009
Tipo del documento:
Article