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Query: UMLS:C0017168 (
gastroesophageal reflux disease
)
11,783
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Obesity and gastro-
oesophageal reflux
are the main predisposing factors for oesophageal adenocarcinoma. We have examined the effects of transient acid exposure and leptin on OE33 oesophageal adenocarcinoma cells. Leptin and acid individually stimulated proliferation and inhibited apoptosis and the combination was synergistic. Leptin receptor protein levels were unchanged by acid exposure. The COX-2 inhibitor NS 398 blocked the effects of acid and leptin but while both acid and leptin individually significantly increased PGE2 production and COX-2 mRNA levels, the combination was not more effective than either stimulant alone. Leptin synergistically enhanced acid-stimulated EGFR and
ERK
phosphorylation but did not further increase JNK or p38 MAP kinase phosphorylation. Specific EGFR and
ERK
inhibitors reduced the effects of leptin and acid alone and in combination. The combination of increased circulating leptin levels in obesity and transient reflux of gastric acid may promote oesophageal carcinogenesis by increasing proliferation and inhibiting apoptosis.
...
PMID:Leptin synergistically enhances the anti-apoptotic and growth-promoting effects of acid in OE33 oesophageal adenocarcinoma cells in culture. 1761 45
The role of weak acids with pH values in the range of 4-7 has been implicated in the symptoms of
gastroesophageal reflux disease
(
GERD
). Prostaglandin E
2
(PGE
2
) is associated with heartburn symptom in
GERD
patients; however, the precise productive mechanisms remain unclear. In this study, we revealed that exposure to weak acids increases PGE
2
production with a peak at pH 4-5, slightly in human normal oesophageal cells (Het-1A), and robustly in oesophageal squamous carcinoma cells (KYSE-270). Release of PGE
2
from the oesophageal mucosa was augmented by weak acid treatment in rat. Chenodeoxycholic acid (CDCA), a bile acid, upregulated cyclooxygenase-2 (COX-2) expression in Het-1A and KYSE-270 and induced PGE
2
production in KYSE-270 cells. Weak acid-induced PGE
2
production was significantly inhibited by cytosolic phospholipase A2 (cPLA2),
ERK
, and transient receptor potential cation channel subfamily V member 4 (TRPV4), a pH-sensing ion channel, inhibitors. Hangeshashinto, a potent inhibitor of COX-2, strongly decreased weak acid- and CDCA-induced PGE
2
levels in KYSE-270. These results indicated that weak acids induce PGE
2
production via TRPV4/
ERK
/cPLA2 in oesophageal epithelial cells, suggesting a role in
GERD
symptoms like heartburn. Interventions targeting pH values up to 5 may be necessary for the treatment of
GERD
.
...
PMID:Weak acids induce PGE
2
production in human oesophageal cells: novel mechanisms underlying GERD symptoms. 3324 92
