Source:http://linkedlifedata.com/resource/pubmed/id/20583136
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2010-7-5
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pubmed:abstractText |
Adiponectin (APN)-mediated cyclooxygenase (COX)-2 induction is known to have various protective effects on cardiovascular diseases. However, the molecular mechanisms of APN-mediated COX-2 induction and its protection against iron-mediated injury in hepatocytes are still unclear. Herein, we show that AMP-mediated peroxisome proliferator-activated receptor (PPAR)alpha activation was attributable to COX-2 induction by APN, which was further confirmed by identifying novel functional PPAR responsive elements (PPREs) in the mouse COX-2 promoter region. Prostaglandin (PG)I2 and PGE2, metabolites of COX-2, time-dependently increased in hepatocytes treated with APN. Interestingly, beraprost and misoprostol, respective agonists for PGI2 and PGE2, mimicked the protective effects of APN in iron-mediated inflammation in hepatocytes. The iron dextran-activated nuclear factor (NF)-kappaB pathway was correlated with the increased production of inflammatory cytokines including tumor necrosis factor-alpha, intercellular adhesion molecule-1, and monocyte chemotactic protein-1. This was eliminated by administration of APN, whereas blockage of PPARalpha activation, an upstream regulator of COX-2 induction by APN, and COX-2 activation reversed the anti-inflammatory effect of APN, suggesting the crucial role of COX-2 in this event. Herein, we demonstrate that APN-mediated COX-2 induction through a PPARalpha-dependent mechanism, and COX-2 exerted an anti-inflammatory effect of APN in hepatocytes subjected to iron challenge.
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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/Adiponectin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Epoprostenol,
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR alpha,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1097-4652
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pubmed:author | |
pubmed:copyrightInfo |
(c) 2010 Wiley-Liss, Inc.
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pubmed:issnType |
Electronic
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pubmed:volume |
224
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
837-47
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pubmed:meshHeading |
pubmed-meshheading:20583136-Adiponectin,
pubmed-meshheading:20583136-Animals,
pubmed-meshheading:20583136-Apoptosis,
pubmed-meshheading:20583136-Cyclooxygenase 2,
pubmed-meshheading:20583136-Dinoprostone,
pubmed-meshheading:20583136-Enzyme Activation,
pubmed-meshheading:20583136-Enzyme Induction,
pubmed-meshheading:20583136-Epoprostenol,
pubmed-meshheading:20583136-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:20583136-Hepatocytes,
pubmed-meshheading:20583136-Humans,
pubmed-meshheading:20583136-Iron,
pubmed-meshheading:20583136-Mice,
pubmed-meshheading:20583136-PPAR alpha,
pubmed-meshheading:20583136-Promoter Regions, Genetic,
pubmed-meshheading:20583136-RNA, Small Interfering,
pubmed-meshheading:20583136-Signal Transduction
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pubmed:year |
2010
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pubmed:articleTitle |
Mechanisms of adiponectin-mediated COX-2 induction and protection against iron injury in mouse hepatocytes.
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pubmed:affiliation |
Department of Otolaryngology, Taipei Medical University-Shuang-Ho Hospital, Taipei, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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