Overexpression of a 60-kDa heat shock protein enhances cytoprotective function of small intestinal epithelial cells

• Published in: Life sciences (1973) Vol. 86; no. 13; pp. 499 - 504
• Main Authors: Takada, Makiko, Otaka, Michiro, Takahashi, Taiji, Izumi, Yuko, Tamaki, Kumiko, Shibuya, Tomoyoshi, Sakamoto, Naoto, Osada, Taro, Yamamoto, Sou, Ishida, Ryuichi, Odashima, Masaru, Itoh, Hideaki, Watanabe, Sumio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 27.03.2010
• Subjects: Animals; Apoptosis; Cell Line; Cell Survival; Chaperonin 60 - metabolism; Cloning, Molecular; Epithelial Cells - metabolism; Gene Expression; HSP60; HSP70; HSP70 Heat-Shock Proteins - metabolism; Humans; Indomethacin; Intestine, Small - injuries; Intestine, Small - metabolism; NSAID; Rats; Small intestinal epithelial cells; HSP60; HSP70; Indomethacin; NSAID; Apoptosis; Small intestinal epithelial cells
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2010.02.010

With the advancement of small intestinal (double balloon and capsule) endoscopy technology, incidence of small intestinal lesion caused by nonsteroidal anti-inflammatory drugs (NSAIDs) has been known to be high. However, therapy for small intestinal mucosal lesion has not yet been developed. Previous studies have shown that heat shock proteins (HSPs) are involved in cytoprotection mediated by their function as a molecular chaperone. In this study, we examined the effect of HSP60 or HSP70 overexpression on hydrogen peroxide-induced (H 2O 2) or indomethacin-induced cell damage in the small intestinal epithelial cells. cDNA of human HSP60 or HSP70 was transfected to rat small intestinal (IEC-6) cells, and HSP60- or HSP70-overexpressing cells were cloned. IEC-6 cells transfected with vector only were used as control cells. These cells were treated with H 2O 2 (0–0.14 mM) or indomethacin (0–2.5 mM). The cell viability was determined by MTT-assay. Cell necrosis was evaluated by LDH-release assay. Further, apoptosis was evaluated by caspases-3/7 activity and TUNEL assay. Cell viability after H 2O 2 or indomethacin treatment was significantly higher in HSP60-overexpressing cells compared with that in control cells and HSP60-overexpressing cells. Apoptotic cells were also reduced in HSP60-overexpressing. Conclusion: These results indicate that HSP60 plays an important role in protecting small intestinal mucosal cells from H 2O 2-induced or indomethacin-induced cell injury. HSP70-overexpressing cells did not show anti-apoptotic ability. These findings possibly suggest that function of each HSP is different in the small intestine. Therefore, for the therapy of small intestinal mucosal lesion, HSP60-induction therapy could be a new therapeutic strategy.