Involvement of ERK AND p38 MAP kinase in AAPH-induced COX-2 expression in HaCaT cells.

Cyclooxygenase-2 (COX-2) appears to play an important role in inflammation and carcinogenesis, and 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) is a hydrophilic azo compound known to generate free radicals. Because reactive oxygen species (ROS) are known to elevate COX-2 expression, we evaluated the effect of AAPH on the expression of COX-2 in a human keratinocyte cell line, HaCaT. When cells were exposed to AAPH, marked COX-2 induction was observed. To clarify the signaling mechanism involved, we next investigated the effects of AAPH upon three major subfamilies of the mitogen-activated protein kinases (MAPKs). AAPH caused an increase in the phosphorylation of extracellular signal-regulated kinase (ERK), p38 and c-Jun NH(2)-terminal kinase (JNK). Furthermore, we found that PD98059, an ERK pathway inhibitor, and SB203580, a p38 MAPK inhibitor, diminished AAPH-induced COX-2 expression and PGE(2) production, whereas JNK inhibitor did not suppress COX-2 expression or PGE(2) production by AAPH. These findings suggest that the ERK and p38 MAPK pathways, but not the JNK pathway, are involved in AAPH-induced inflammatory progression. In addition, we found that both the water-soluble Vitamin E derivative, Trolox, and the green tea constituent, (-)-epigallocatechin gallate (EGCG), diminished AAPH-induced COX-2 expression and p38 activation.
AuthorsYong Cui, Dong-Seok Kim, Seo-Hyoung Park, Jin-A Yoon, Soon-Kyum Kim, Sun-Bang Kwon, Kyoung-Chan Park
JournalChemistry and physics of lipids (Chem Phys Lipids) Vol. 129 Issue 1 Pg. 43-52 (Apr 2004) ISSN: 0009-3084 [Print] Ireland
PMID14998726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Amidines
  • Chromans
  • Enzyme Inhibitors
  • Flavonoids
  • Free Radical Scavengers
  • Imidazoles
  • Isoenzymes
  • Membrane Proteins
  • Pyridines
  • SB 203580
  • 2,2'-azobis(2-amidinopropane)
  • Catechin
  • epigallocatechin gallate
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • Dinoprostone
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
  • Amidines (pharmacology)
  • Catechin (analogs & derivatives, pharmacology)
  • Chromans (pharmacology)
  • Cyclooxygenase 2
  • Dinoprostone (biosynthesis)
  • Enzyme Induction (drug effects)
  • Enzyme Inhibitors (pharmacology)
  • Flavonoids (pharmacology)
  • Free Radical Scavengers (pharmacology)
  • Humans
  • Imidazoles (pharmacology)
  • Isoenzymes (biosynthesis, drug effects)
  • JNK Mitogen-Activated Protein Kinases
  • Keratinocytes (enzymology)
  • MAP Kinase Kinase 4
  • Membrane Proteins
  • Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors, metabolism)
  • Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
  • Prostaglandin-Endoperoxide Synthases (biosynthesis, drug effects)
  • Pyridines (pharmacology)
  • p38 Mitogen-Activated Protein Kinases

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