Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-7-5
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1097-4652
pubmed:author
pubmed:copyrightInfo
(c) 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
224
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
837-47
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Mechanisms of adiponectin-mediated COX-2 induction and protection against iron injury in mouse hepatocytes.
pubmed:affiliation
Department of Otolaryngology, Taipei Medical University-Shuang-Ho Hospital, Taipei, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't