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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2000-2-29
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pubmed:abstractText |
Hypoxic injury provokes inflammation of many tissues including the ocular surface. In rabbit corneal epithelial cells, both peroxisome proliferator-activated receptor (PPAR)-inducible cytochrome P450 4B1 and cyclooxygenase-2 (COX-2) mRNAs were increased by hypoxia. PPAR alpha and beta but not gamma mRNAs were detected in these cells. The PPAR activator, WY-14,643 increased COX-2 expression. Similarly, non-steroidal anti-inflammatory drugs with the ability to activate PPARs induced COX-2 independently of prostaglandin synthesis inhibition. COX-2 protein overexpression by hypoxia and PPAR activation was not associated with a parallel increase in prostaglandin E(2) accumulation. However, the enzyme regained full catalytic activity when: 1) hypoxic cells were re-exposed to normoxic conditions in the presence of heme and arachidonic acid, and 2) WY-14,643-treated cells were depleted of intracellular GSH. Consistent with previous observations showing that the corneal production of cytochrome P450-derived inflammatory eicosanoids is elevated by hypoxia and inflammation, the current data suggest that hypoxic injury is a model of inflammation in which molecules other than COX-derived arachidonic acid metabolites play a major proinflammatory role. This study also suggests that increased cellular GSH may be the mechanism responsible for the characteristic dissociation of PPAR-induced COX-2 expression and activity. Moreover, we provide new insights into the commonly observed lack of efficacy of classical non-steroidal anti-inflammatory drugs in the treatment of hypoxia-related ocular surface inflammation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxisome Proliferators,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/cytochrome P-450 CYP4B1,
http://linkedlifedata.com/resource/pubmed/chemical/pirinixic acid
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2837-44
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10644750-Animals,
pubmed-meshheading:10644750-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:10644750-Base Sequence,
pubmed-meshheading:10644750-Cell Hypoxia,
pubmed-meshheading:10644750-Cell Line,
pubmed-meshheading:10644750-Cyclooxygenase 2,
pubmed-meshheading:10644750-Cytochrome P-450 Enzyme System,
pubmed-meshheading:10644750-DNA Primers,
pubmed-meshheading:10644750-Dinoprostone,
pubmed-meshheading:10644750-Epithelium, Corneal,
pubmed-meshheading:10644750-Isoenzymes,
pubmed-meshheading:10644750-Peroxisome Proliferators,
pubmed-meshheading:10644750-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:10644750-Pyrimidines,
pubmed-meshheading:10644750-RNA, Messenger,
pubmed-meshheading:10644750-Rabbits,
pubmed-meshheading:10644750-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:10644750-Transcription Factors,
pubmed-meshheading:10644750-Transcriptional Activation
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pubmed:year |
2000
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pubmed:articleTitle |
Regulation of cyclooxygenase-2 by hypoxia and peroxisome proliferators in the corneal epithelium.
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pubmed:affiliation |
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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