Rebamipide, a Gastroprotective Drug, Inhibits Indomethacin-Induced Apoptosis in Cultured Rat Gastric Mucosal Cells: Association with the Inhibition of Growth Arrest and DNA Damage-Induced 45 Expression

Authors: Naito, Yuji¹; Kajikawa, Hirokazu²; Mizushima, Katsura²; Shimozawa, Makoto²; Kuroda, Masaaki²; Katada, Kazuhiro²; Takagi, Tomohisa²; Handa, Osamu³; Kokura, Satoshi³; Ichikawa, Hiroshi⁴; Yoshida, Norimasa⁵; Matsui, Hirofumi⁶; Yoshikawa, Toshikazu²

Source: Digestive Diseases and Sciences, Volume 50, Supplement 1, October 2005 , pp. S104-S112(9)

Publisher: Springer

Abstract:

Rebamipide, a gastromucosal protective drug, suppresses indomethacin-induced gastropathy in humans and rodents. Effects of rebamipide on gene expression in indomethacin-treated gastric mucosal cells (RGM1) were investigated using high-density oligonucleotide arrays. Indomethacin induced apoptosis in RGM1 cells in a dose-dependent manner. Rebamipide pretreatment significantly reduced indomethacin-induced apoptosis. We used gene expression profiling on high-density oligonucleotide probe arrays to characterize the transcriptional response of RGM1 cells to indomethacin treatment for 6 hr. Of the 8,799 probes examined, 717 (8.1%) were induced (400 probes) or repressed (317 probes) at least 1.5-fold. Among the 158 genes that were induced by indomethacin at least 2.0-fold, four genes that were down-regulated by rebamipide at least 2.0-fold are listed: growth arrest and DNA-damage-inducible 45 (GADD45), golgi SNAP receptor complex member 1, iodothyronine deiodinases, and transcription factor 8. Real time-PCR confirmed GADD45 expression and its inhibition by rebamipide. Inhibition of apoptosis-related genes is possibly important for the cytoprotective effect of rebamipide against indomethacin-induced gastric mucosal cell injury.

Keywords: apoptosis; DNA microarray; GADD45; indomethacin; rebamipide

Document Type: Research article

DOI: http://dx.doi.org/10.1007/s10620-005-2814-3

Affiliations: 1: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan, Email: ynaito@koto.kpu-m.ac.jp 2: Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, 3: Department of Biomedical Safety Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, 4: Department of Food Sciences and Nutritional Health, The Faculty of Human Environment, Kyoto Prefectural University, Kyoto, 606-8522, 5: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan, 6: Division of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan,

Publication date: 2005-10-01

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• In this Subject: Gastroenterology
• By this author: Naito, Yuji ;  Kajikawa, Hirokazu ;  Mizushima, Katsura ;  Shimozawa, Makoto ;  Kuroda, Masaaki ;  Katada, Kazuhiro ;  Takagi, Tomohisa ;  Handa, Osamu ;  Kokura, Satoshi ;  Ichikawa, Hiroshi ;  Yoshida, Norimasa ;  Matsui, Hirofumi ;  Yoshikawa, Toshikazu

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