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KMID : 0043320110340101759
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Archives of Pharmacal Research
2011 Volume.34 No. 10 p.1759 ~ p.1768
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The mechanism of MAP kinase activation under acidic condition in feline esophageal smooth muscle cells
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Park Sun-Young
Lee Young-Ju
Min Young-Sil
Kim Hak-Rim
Jeong Ji-Hoon
Sohn Uy-Dong
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Abstract
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Reflux esophagitis results from repeated exposure of the esophagus to acidic gastric juice or bile-containing duodenal contents. In Barrett’s adenocarcinoma, acid increases proliferation via ERK and p38 MAPK activation. This study was focused on determination of the mechanism(s) underlying MAPKs (ERK 1/2, p38 MAPK, and JNK) activation induced by acidic medium at pH 4 in normal feline primary cultured esophageal smooth muscle cells (FESMCs). We detected ERK 1/2 and p38 MAPK phosphorylation after exposure to pH 4 or neutral media in the presence or absence of several inhibitors and quantified the MAPK levels using western blotting analysis and densitometry. Acidic medium markedly increased the phosphorylation of ERK 1/2 and p38 MAPK within 10 min. Acid-induced ERK 1/2 and p38 MAPK activation was inhibited by pertussis toxin (PTX-sensitive Gi/o protein inhibitor), DEDA (phospholipase (PL) A2 inhibitor), ρCMB (PLD inhibitor), GF109203X (protein kinase C (PKC) inhibitor) and D609 (phosphatidylcholinespecific PLC inhibitor). But, genistein (tyrosine kinase inhibitor), forskolin (adenylate cyclase activator) and U73122 (phosphatidylinositol-specific PLC inhibitor) had no effect on acidinduced ERK1/2 and p38 MAPK activation. These findings indicate that the activation of ERK 1/2 and p38 MAPK pathways by acidic conditions, at least in part, may be mediated by activation of the Gi/o protein coupled receptors, PC-PLC, PLD, PLA2, and PKC in FESMCs.
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KEYWORD
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Esophageal epithelial cell, Acid, ERK 1/2, p38 MAPK, Reflux esophagitis, Signal transduction
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