Suppression of indomethacin-induced apoptosis in the small intestine due to Bach1 deficiency

Akihito Harusato, Yuji Naito, Tomohisa Takagi, Kazuhiko Uchiyama, Katsura Mizushima, Yasuko Hirai, Shinya Yamada, Toshifumi Tuji, Hiroyuki Yoriki, Ryusuke Horie, Ken Inoue, Kohei Fukumoto, Osamu Handa, Takeshi Ishikawa, Satoshi Kokura, Yukiko Minamiyama, Hiroshi Ichikawa, Akihiko Muto, Kazuhiko Igarashi, Toshikazu Yoshikawa

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

BTB and CNC homologue 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1). This study hypothesized that Bach1 plays an important role in the indomethacin-induced apoptosis in the case of small-intestinal mucosal injury. Eight-week-old male C57BL/6 (wild-type) and homozygous Bach1-deficient C57BL/6 mice were included in this study. Mucosal injuries induced by subcutaneously administering indomethacin were evaluated macroscopically, histologically and biochemically. Indomethacin-induced injuries were improved in Bach1-deficient mice. Immunohistochemistry showed an increase in the number of HO-1-positive cells, which were mainly F4/80 positive macrophages, in Bach1-deficient mice. Indomethacin administration increased the expression of HO-1 mRNA and protein in the small intestine in Bach1-deficient mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining showed that the extent of apoptosis was suppressed in Bach1-deficent mice. In conclusion, deficiency of the Bach1 gene inhibited apoptosis and thus suppressed mucosal injury, indicating that Bach1 is a novel therapeutic target for indomethacin-induced intestinal injury.

Original languageEnglish
Pages (from-to)717-727
Number of pages11
JournalFree Radical Research
Volume45
Issue number6
DOIs
Publication statusPublished - 2011 Jun

Keywords

  • Bach1
  • Non-steroidal anti-infl ammatory drugs
  • apoptosis
  • heme oxygenase-1
  • small intestine

ASJC Scopus subject areas

  • Biochemistry

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