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

doi:10.3109/10715762.2011.574287

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

MED - Medical Sciences

Research output: Contribution to journal › Article › peer-review

23 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 language	English
Pages (from-to)	717-727
Number of pages	11
Journal	Free Radical Research
Volume	45
Issue number	6
DOIs	https://doi.org/10.3109/10715762.2011.574287
Publication status	Published - 2011 Jun

Keywords

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

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10.3109/10715762.2011.574287

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Harusato, A., Naito, Y., Takagi, T., Uchiyama, K., Mizushima, K., Hirai, Y., Yamada, S., Tuji, T., Yoriki, H., Horie, R., Inoue, K., Fukumoto, K., Handa, O., Ishikawa, T., Kokura, S., Minamiyama, Y., Ichikawa, H., Muto, A., Igarashi, K., & Yoshikawa, T. (2011). Suppression of indomethacin-induced apoptosis in the small intestine due to Bach1 deficiency. Free Radical Research, 45(6), 717-727. https://doi.org/10.3109/10715762.2011.574287

@article{634b0ea1f2b44783beadd5b16e56daf9,

title = "Suppression of indomethacin-induced apoptosis in the small intestine due to Bach1 deficiency",

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.",

keywords = "Bach1, Non-steroidal anti-infl ammatory drugs, apoptosis, heme oxygenase-1, small intestine",

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

note = "Funding Information: This work was supported by a Grant-in-Aid for Scientific Research (B) to T.Y. (no. 21390184) and (C) to Y.N. (no. 22590705) from the Japan Society for the Promotion of Science; by a City Area Program to T.Y. and Y.N. from the Ministry of Education, Culture, Sports, Science and Technology, Japan; and by an Adaptable and Seamless Technology Transfer Program through target-driven R&D to Y.N. from the Japan Science and Technology Agency.",

year = "2011",

month = jun,

doi = "10.3109/10715762.2011.574287",

language = "English",

volume = "45",

pages = "717--727",

journal = "Free Radical Research",

issn = "1071-5762",

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number = "6",

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Harusato, A, Naito, Y, Takagi, T, Uchiyama, K, Mizushima, K, Hirai, Y, Yamada, S, Tuji, T, Yoriki, H, Horie, R, Inoue, K, Fukumoto, K, Handa, O, Ishikawa, T, Kokura, S, Minamiyama, Y, Ichikawa, H, Muto, A , Igarashi, K & Yoshikawa, T 2011, 'Suppression of indomethacin-induced apoptosis in the small intestine due to Bach1 deficiency', Free Radical Research, vol. 45, no. 6, pp. 717-727. https://doi.org/10.3109/10715762.2011.574287

TY - JOUR

T1 - Suppression of indomethacin-induced apoptosis in the small intestine due to Bach1 deficiency

AU - Harusato, Akihito

AU - Naito, Yuji

AU - Takagi, Tomohisa

AU - Uchiyama, Kazuhiko

AU - Mizushima, Katsura

AU - Hirai, Yasuko

AU - Yamada, Shinya

AU - Tuji, Toshifumi

AU - Yoriki, Hiroyuki

AU - Horie, Ryusuke

AU - Inoue, Ken

AU - Fukumoto, Kohei

AU - Handa, Osamu

AU - Ishikawa, Takeshi

AU - Kokura, Satoshi

AU - Minamiyama, Yukiko

AU - Ichikawa, Hiroshi

AU - Muto, Akihiko

AU - Igarashi, Kazuhiko

AU - Yoshikawa, Toshikazu

N1 - Funding Information: This work was supported by a Grant-in-Aid for Scientific Research (B) to T.Y. (no. 21390184) and (C) to Y.N. (no. 22590705) from the Japan Society for the Promotion of Science; by a City Area Program to T.Y. and Y.N. from the Ministry of Education, Culture, Sports, Science and Technology, Japan; and by an Adaptable and Seamless Technology Transfer Program through target-driven R&D to Y.N. from the Japan Science and Technology Agency.

PY - 2011/6

Y1 - 2011/6

N2 - 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.

AB - 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.

KW - Bach1

KW - Non-steroidal anti-infl ammatory drugs

KW - apoptosis

KW - heme oxygenase-1

KW - small intestine

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U2 - 10.3109/10715762.2011.574287

DO - 10.3109/10715762.2011.574287

M3 - Article

C2 - 21473739

AN - SCOPUS:79959455144

SN - 1071-5762

VL - 45

SP - 717

EP - 727

JO - Free Radical Research

JF - Free Radical Research

IS - 6

ER -

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

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Keywords

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