Rebamipide induces the gastric mucosal protective factor, cyclooxygenase-2, via activation of 5′-AMP-activated protein kinase

Sunyoung Lee, Seongkeun Jeong, Wooseong Kim, Dohoon Kim, Yejin Yang, Jeong Hyun Yoon, Byung Joo Kim, Do Sik Min, Yunjin Jung

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Rebamipide, an amino acid derivative of 2(1H)-quinolinone, has been used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. Induction of cyclooxygenase (COX)-2, a gastric mucosal protective factor, by rebamipide has been suggested as the major mechanism of the drug action. However, how rebamipide induces COX-2 at the molecular level needs further investigation. In this study, the molecular mechanism underlying the induction of COX-2 by rebamipide was investigated. In gastric carcinoma cells and macrophage cells, rebamipide induced phosphorylation of AMP-activated protein kinase (AMPK), leading to phosphorylation of acetyl-CoA carboxylase (ACC), a substrate of AMPK. The induction of COX-2 by rebamipide was dependent on AMPK activation because compound C, an AMPK inhibitor, abolished COX-2 induction by rebamipide. In a mouse ulcer model, rebamipide protected against hydrochloric acid/ethanol-induced gastric ulcer, and these protective effects were deterred by co-administration of compound C. In parallel, in the gastric tissues, rebamipide increased the phosphorylation AMPK, whereas compound C reduced the levels of COX-2 and phosphorylated ACC, which were increased by rebamipide. Taken together, the activation of AMPK by rebamipide may be a molecular mechanism that contributes to induction of COX-2, probably resulting in protection against gastric ulcers.

Original languageEnglish
Pages (from-to)449-455
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume483
Issue number1
DOIs
Publication statusPublished - 2017 Jan 29

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AMP-Activated Protein Kinases
Cyclooxygenase 2
Stomach
Chemical activation
Phosphorylation
Acetyl-CoA Carboxylase
Stomach Ulcer
rebamipide
Protective Factors
Hydrochloric Acid
Macrophages
Quinolones
Gastritis
Protein Kinase Inhibitors
Peptic Ulcer
Ulcer
Ethanol
Cells
Tissue
Derivatives

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, Sunyoung ; Jeong, Seongkeun ; Kim, Wooseong ; Kim, Dohoon ; Yang, Yejin ; Yoon, Jeong Hyun ; Kim, Byung Joo ; Min, Do Sik ; Jung, Yunjin. / Rebamipide induces the gastric mucosal protective factor, cyclooxygenase-2, via activation of 5′-AMP-activated protein kinase. In: Biochemical and Biophysical Research Communications. 2017 ; Vol. 483, No. 1. pp. 449-455.
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Rebamipide induces the gastric mucosal protective factor, cyclooxygenase-2, via activation of 5′-AMP-activated protein kinase. / Lee, Sunyoung; Jeong, Seongkeun; Kim, Wooseong; Kim, Dohoon; Yang, Yejin; Yoon, Jeong Hyun; Kim, Byung Joo; Min, Do Sik; Jung, Yunjin.

In: Biochemical and Biophysical Research Communications, Vol. 483, No. 1, 29.01.2017, p. 449-455.

Research output: Contribution to journalArticle

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T1 - Rebamipide induces the gastric mucosal protective factor, cyclooxygenase-2, via activation of 5′-AMP-activated protein kinase

AU - Lee, Sunyoung

AU - Jeong, Seongkeun

AU - Kim, Wooseong

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