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

• Published in: Free radical research Vol. 45; no. 6; pp. 717 - 727
• Main Authors: Harusato, Akihito, Naito, Yuji, Takagi, Tomohisa, Uchiyama, Kazuhiko, Mizushima, Katsura, Hirai, Yasuko, Yamada, Shinya, Tuji, Toshifumi, Yoriki, Hiroyuki, Horie, Ryusuke, Inoue, Ken, Fukumoto, Kohei, Handa, Osamu, Ishikawa, Takeshi, Kokura, Satoshi, Minamiyama, Yukiko, Ichikawa, Hiroshi, Muto, Akihiko, Igarashi, Kazuhiko, Yoshikawa, Toshikazu
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.06.2011; Taylor & Francis
• Subjects: Animals; apoptosis; Apoptosis - drug effects; Bach1; Basic-Leucine Zipper Transcription Factors - deficiency; Basic-Leucine Zipper Transcription Factors - genetics; Caspase 3 - metabolism; Enzyme Activation; Enzyme Assays; Gene Deletion; heme oxygenase-1; Heme Oxygenase-1 - antagonists & inhibitors; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Ileum - drug effects; Ileum - metabolism; Ileum - pathology; Indomethacin - adverse effects; Male; Metalloporphyrins - pharmacology; Mice; Mice, Inbred C57BL; Non-steroidal anti-inflammatory drugs; Protoporphyrins - pharmacology; small intestine; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Ulcer - chemically induced; Ulcer - pathology
• ISSN: 1071-5762; 1029-2470
• DOI: 10.3109/10715762.2011.574287

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.