tailieunhanh - Báo cáo khoa học: Identification of sodium salicylate as an hsp inducer using a simple screening system for stress response modulators in mammalian cells

Asheat shockproteins (Hsps) are involved inprotecting cells and also in the pathophysiology of diseases such as inflam-mation, cancer and neurodegenerative disorders, modula-tors ofHsp expression inmammalian cells would seemto be useful for the treatment of various diseases. In this study, we isolated mammalian cell lines for screening of Hsp modu-lators; mouse C3H10T1/2 cells stably transfected with a plasmid containing the mouse Hsp105 or human Hsp70B promoter upstream of a luciferase or b-galactosidase reporter gene, respectively | Eur. J. Biochem. 270 3461-3468 2003 FEBS 2003 doi Identification of sodium salicylate as an hsp inducer using a simple screening system for stress response modulators in mammalian cells Keiichi Ishihara Kenji Horiguchi Nobuyuki Yamagishi and Takumi Hatayama Department of Biochemistry Kyoto Pharmaceutical University Japan As heat shock proteins Hsps are involved in protecting cells and also in the pathophysiology of diseases such as inflammation cancer and neurodegenerative disorders modulators of Hsp expression in mammalian cells would seem to be useful for the treatment of various diseases. In this study we isolated mammalian cell lines for screening of Hsp modulators mouse C3H10T1 2 cells stably transfected with a plasmid containing the mouse Hsp105 or human Hsp70B promoter upstream of a luciferase or b-galactosidase reporter gene respectively. Using these cells we examined the effect of sodium salicylate SA which may induce the transcription of hsp genes on stress response in mammalian cells. When these cells were treated with SA for 1 h at 37 C both promoter activities were up-regulated by SA at concentrations of more than 45 mM. The activation of heat shock factor and the subsequent accumulation of Hsp105a and Hsp70 were detected in cells treated with SA at concentrations of more than 20 and 45 mM respectively. Furthermore SA induced resistance against a subsequent lethal stress. These findings suggested that SA is a potent hsp inducer and may be used to protect cells against deleterious stressors. Keywords cytoprotection heat shock factor heat shock promoter heat shock proteins sodium salicylate. Heat shock proteins Hsp are a set of highly conserved proteins that are produced in response to physiological and environmental stress 1 . Hsps are also expressed under physiological conditions and play important roles in normal cellular events such as the synthesis translocation and degradation of proteins 2 . Hsps protect cells from