Carbenoxolone Induces Hsp70 via HSF1 activation

• Published in: Japanese Journal of Pharmacology 2000, Vol.82 (suppl.1), p.104-104
• Main Authors: Shin-ichi Nagayama, Hirofumi Kai, Harumi Suzaki, Kikuko Sakai, Eri Tsuruya, Takeshi Miyata, Isao Yamatsu
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

The induction of heat shock protein 70 (Hsp70) is one of the best known mechanisms protecting cells from various harmful stresses. Substantial evidence indicates that Hsp70 is capable of protecting cells, tissues, organs, and animals from a subsequent, normally lethal heating, as well as from numerous disease states. Therefore, it would be of great therapeutic benefit to discover compounds that are clinically safe yet able to induce Hsp70 in patients. Carbenoxolone, an antiulcer drug, protects gastric mucosal cells to irritants in vivo and in vitro. We assessed here whether carbenoxolone induces Hsp70 expression in several human cell lines. We found that carbenoxolone increased Hsp70 protein and mRNA, Hsp70 promoter activity, and DNA-binding activity of human heat shock factor1 (HSF1). Rtrther, carbenoxolone increased HSF1 protein and HSF1 phosphorylation, and inhibited cell death induced by a lethal heat shock. Thus, we provide evidence that carbenoxolone induces Hsp70 expression via HSF1 activation, suggesting that cytoprotective effect by carbenoxolone is caused by the induction of Hsp70.