Prostaglandin E2 protects gastric mucosal cells from apoptosis via EP2 and EP4 receptor activation

Tatsuya Hoshino, Shinji Tsutsumi, Wataru Tomisato, Hyun Jung Hwang, Tomofusa Tsuchiya, Tohru Mizushima

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131 Citations (Scopus)


Prostaglandin E2 (PGE2) has a strong protective effect on the gastric mucosa in vivo; however, the molecular mechanism of a direct cytoprotective effect of PGE2 on gastric mucosal cells has yet to be elucidated. Although we reported previously that PGE2 inhibited gastric irritant-induced apoptotic DNA fragmentation in primary cultures of guinea pig gastric mucosal cells, we show here that PGE2 inhibits the ethanol-dependent release of cytochrome c from mitochondria. Of the four main subtypes of PGE2 receptors, we also demonstrated, using subtype-specific agonists, that EP2 and EP4 receptors are involved in the PGE2-mediated protection of gastric mucosal cells from ethanol-induced apoptosis. Activation of EP2 and EP4 receptors is coupled with an increase in cAMP, for which a cAMP analogue was found here to inhibit the ethanol-induced apoptosis. The increase in cAMP is known to activate both protein kinase A (PKA) and phosphatidylinositol 3-kinase pathways. An inhibitor of PKA but not of phosphatidylinositol 3-kinase blocked the PGE2-mediated protection of cells from ethanol-induced apoptosis, suggesting that a PKA pathway is mainly responsible for the PGE2-mediated inhibition of apoptosis. Based on these results, we considered that PGE2 inhibited gastric irritant-induced apoptosis in gastric mucosal cells via induction of an increase in cAMP and activation of PKA, and that this effect was involved in the PGE2-mediated protection of the gastric mucosa from gastric irritants in vivo.

Original languageEnglish
Pages (from-to)12752-12758
Number of pages7
JournalJournal of Biological Chemistry
Issue number15
Publication statusPublished - 2003 Apr 11
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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