Mechanisms of adiponectin-mediated COX-2 induction and protection against iron injury in mouse hepatocytes

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Abstract

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)α 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-2promoter 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)-κB pathway was correlated with the increased production of inflammatory cytokines including tumor necrosis factor-α, intercellular adhesion molecule-1, and monocyte chemotactic protein-1. This was eliminated by administration of APN, whereas blockage of PPARα 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 PPARα-dependent mechanism, and COX-2 exerted an anti-inflammatory effect of APN in hepatocytes subjected to iron challenge.

Original languageEnglish
Pages (from-to)837-847
Number of pages11
JournalJournal of Cellular Physiology
Volume224
Issue number3
DOIs
Publication statusPublished - Sep 2010

Fingerprint

Adiponectin
Cyclooxygenase 2
Hepatocytes
Iron
Wounds and Injuries
Peroxisome Proliferator-Activated Receptors
beraprost
Chemical activation
Epoprostenol
Dinoprostone
Anti-Inflammatory Agents
Misoprostol
Chemokine CCL2
Intercellular Adhesion Molecule-1
Adenosine Monophosphate
Prostaglandin-Endoperoxide Synthases
Metabolites
Dextrans
Cardiovascular Diseases
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

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title = "Mechanisms of adiponectin-mediated COX-2 induction and protection against iron injury in mouse hepatocytes",
abstract = "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)α 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-2promoter 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)-κB pathway was correlated with the increased production of inflammatory cytokines including tumor necrosis factor-α, intercellular adhesion molecule-1, and monocyte chemotactic protein-1. This was eliminated by administration of APN, whereas blockage of PPARα 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 PPARα-dependent mechanism, and COX-2 exerted an anti-inflammatory effect of APN in hepatocytes subjected to iron challenge.",
author = "Lee, {Fei Peng} and Jen, {Chih Yu} and Chang, {Chih Cheng} and Ying Chou and Heng Lin and Chou, {Chih Ming} and Juan, {Shu Hui}",
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T1 - Mechanisms of adiponectin-mediated COX-2 induction and protection against iron injury in mouse hepatocytes

AU - Lee, Fei Peng

AU - Jen, Chih Yu

AU - Chang, Chih Cheng

AU - Chou, Ying

AU - Lin, Heng

AU - Chou, Chih Ming

AU - Juan, Shu Hui

PY - 2010/9

Y1 - 2010/9

N2 - 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)α 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-2promoter 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)-κB pathway was correlated with the increased production of inflammatory cytokines including tumor necrosis factor-α, intercellular adhesion molecule-1, and monocyte chemotactic protein-1. This was eliminated by administration of APN, whereas blockage of PPARα 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 PPARα-dependent mechanism, and COX-2 exerted an anti-inflammatory effect of APN in hepatocytes subjected to iron challenge.

AB - 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)α 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-2promoter 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)-κB pathway was correlated with the increased production of inflammatory cytokines including tumor necrosis factor-α, intercellular adhesion molecule-1, and monocyte chemotactic protein-1. This was eliminated by administration of APN, whereas blockage of PPARα 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 PPARα-dependent mechanism, and COX-2 exerted an anti-inflammatory effect of APN in hepatocytes subjected to iron challenge.

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