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

Abstract

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.

• Authors: Yong Cui, Dong-Seok Kim, Seo-Hyoung Park, Jin-A Yoon, Soon-Kyum Kim, Sun-Bang Kwon, Kyoung-Chan Park
• Journal: Chemistry and physics of lipids (Chem Phys Lipids) Vol. 129 Issue 1 Pg. 43-52 (Apr 2004) ISSN: 0009-3084 [Print] Ireland
• PMID: 14998726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amidines
• Chromans
• Enzyme Inhibitors
• Flavonoids
• Free Radical Scavengers
• Imidazoles
• Isoenzymes
• Membrane Proteins
• Pyridines
• 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
• SB 203580
• 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• 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