Source:http://linkedlifedata.com/resource/pubmed/id/12556459
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
15
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pubmed:dateCreated |
2003-4-7
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pubmed:abstractText |
Prostaglandin E(2) (PGE(2)) has a strong protective effect on the gastric mucosa in vivo; however, the molecular mechanism of a direct cytoprotective effect of PGE(2) on gastric mucosal cells has yet to be elucidated. Although we reported previously that PGE(2) inhibited gastric irritant-induced apoptotic DNA fragmentation in primary cultures of guinea pig gastric mucosal cells, we show here that PGE(2) inhibits the ethanol-dependent release of cytochrome c from mitochondria. Of the four main subtypes of PGE(2) receptors, we also demonstrated, using subtype-specific agonists, that EP(2) and EP(4) receptors are involved in the PGE(2)-mediated protection of gastric mucosal cells from ethanol-induced apoptosis. Activation of EP(2) and EP(4) 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 PGE(2)-mediated protection of cells from ethanol-induced apoptosis, suggesting that a PKA pathway is mainly responsible for the PGE(2)-mediated inhibition of apoptosis. Based on these results, we considered that PGE(2) 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 PGE(2)-mediated protection of the gastric mucosa from gastric irritants in vivo.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Prostaglandin E,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Prostaglandin E, EP2...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Prostaglandin E, EP4...
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12752-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12556459-Animals,
pubmed-meshheading:12556459-Apoptosis,
pubmed-meshheading:12556459-Caspases,
pubmed-meshheading:12556459-Cytochrome c Group,
pubmed-meshheading:12556459-Dinoprostone,
pubmed-meshheading:12556459-Gastric Mucosa,
pubmed-meshheading:12556459-Guinea Pigs,
pubmed-meshheading:12556459-Kinetics,
pubmed-meshheading:12556459-Mitochondria,
pubmed-meshheading:12556459-Receptors, Prostaglandin E,
pubmed-meshheading:12556459-Receptors, Prostaglandin E, EP2 Subtype,
pubmed-meshheading:12556459-Receptors, Prostaglandin E, EP4 Subtype
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pubmed:year |
2003
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pubmed:articleTitle |
Prostaglandin E2 protects gastric mucosal cells from apoptosis via EP2 and EP4 receptor activation.
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pubmed:affiliation |
Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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