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

• Published in: Digestive diseases and sciences Vol. 56; no. 7; pp. 1954 - 1961
• Main Authors: Tamaki, Kumiko, Otaka, Michiro, Takada, Makiko, Yamamoto, Soh, Odashima, Masaru, Itoh, Hideaki, Watanabe, Sumio
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.07.2011; Springer; Springer Nature B.V
• Subjects: Analysis; Animals; Apoptosis - drug effects; Benzoquinones - pharmacology; Biochemistry; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cell Line; Cytoprotection; Enzyme Inhibitors - pharmacology; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gastroenterology; Heat shock proteins; Hepatology; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - biosynthesis; Humans; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Indomethacin; Indomethacin - pharmacology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestine, Small - metabolism; Intestine, Small - pathology; Lactams, Macrocyclic - pharmacology; Medical colleges; Medical sciences; Medicine; Medicine & Public Health; Oncology; Original Article; Pharmacology. Drug treatments; Proteins; Rats; Technology application; Transplant Surgery; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Heat shock proteins; HSP90; Oxidative stress; 17-AAG; Small intestine; NSAIDs; Non steroidal antiinflammatory agent; Gastroenterology; Heat shock protein; Epithelial cell; Metabolic diseases
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-010-1558-x

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.