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Evidence for Enhanced Cytoprotective Function of HSP90-Overexpressing Small Intestinal Epithelial Cells

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Abstract

Background

In the clinical field, increasing incidence of small intestinal ulcers associated with nonsteroidal anti-inflammatory drugs (NSAIDs) has become a topic with the advances of capsule endoscopy and balloon enteroscopy technology for the detection of small intestinal lesions. However, the pathogenesis of NSAID-induced mucosal damage, defensive mechanism of intestinal epithelial cells, and therapy for small intestinal mucosal lesion have not been fully understood. Heat shock proteins (HSPs) are involved in cytoprotection mediated by their function as a molecular chaperone. Since the function of HSP90 in the intestinal epithelial cells has not been well investigated, we examined the cytoprotective ability of HSP90-overexpressing small intestinal epithelial cells against hydrogen peroxide-induced or indomethacin-induced cell damage.

Methods

cDNA of human HSP90 gene was transfected to rat small intestinal epithelial cells (IEC-6 cells), and HSP90-overexpressing cells (IEC-6-90 cells) were selected and cloned. Anti-necrotic abilities and anti-apoptotic abilities of IEC-6-90 cells were compared with IEC-6-mock cells (transfected with vector alone). To examine the specific contribution of HSP90 on cytoprotection of IEC-6-90 cells, cytoprotective ability of IEC-6-90 cells was analyzed with or without pretreatment with functional inhibitor of HSP90, geldanamycine analog, followed by hydrogen peroxide-challenge or indomethacin-challenge.

Results

Hydrogen peroxide-induced or indomethacin-induced cell necrosis and apoptosis were significantly suppressed in IEC-6-90 cells. The cytoprotective ability of IEC-6-90 cells was suppressed by HSP90 inhibitor.

Conclusions

Our results suggest that HSP90 might play an important role in protecting small intestinal epithelial cells from hydrogen peroxide-induced or indomethacin-induced cell injury in vitro, and raised the possibility of protection of small intestinal epithelial cells by manipulation of HSP90 expression.

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Authors and Affiliations

  1. Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan

    Kumiko Tamaki, Michiro Otaka, Makiko Takada & Sumio Watanabe

  2. Department of Life Science, Faculty of Engineering and Resource Science, Akita University, Akita, Japan

    Soh Yamamoto & Hideaki Itoh

  3. Department of Gastroenterology, Yokote Municipal Hospital, Yokote, Japan

    Masaru Odashima

Authors
  1. Kumiko Tamaki
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  2. Michiro Otaka
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  3. Makiko Takada
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  4. Soh Yamamoto
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  5. Masaru Odashima
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  6. Hideaki Itoh
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  7. Sumio Watanabe
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Correspondence to Michiro Otaka.

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Tamaki, K., Otaka, M., Takada, M. et al. Evidence for Enhanced Cytoprotective Function of HSP90-Overexpressing Small Intestinal Epithelial Cells. Dig Dis Sci 56, 1954–1961 (2011). https://doi.org/10.1007/s10620-010-1558-x

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  • DOI: https://doi.org/10.1007/s10620-010-1558-x

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