title: The phenylic hydroxyl group is essential for the induction of stress response by sodium salicylate.
abstract: We have shown that sodium salicylate (SA) activates the heat shock promoter and induces the expression of heat shock proteins (Hsps) with a concomitant increase in the thermotolerance of cells. To identify the functional groups of SA necessary for the induction of Hsps, we evaluated the effect of various derivatives of SA using a mammalian cell line containing a reporter gene downstream of an hsp105 promoter. Among the derivatives, the compounds in which the carboxyl group of SA was substituted activated the hsp105 promoter at 37 degrees C as SA did, but the compounds in which the hydroxyl group was substituted did not. Thus, the phenylic hydroxyl group but not the carboxyl group of SA seemed to be necessary for a stress-induced response. In addition, the orientation of two functional groups on the benzene ring of SA derivatives was also important for the induction of a response. Among these compounds, salicylalcohol which strongly induced the expression of Hsps suppressed the protein aggregation and apoptosis caused by an expanded polyglutamine tract in a cellular model of polyglutamine disease. These findings may aid in the development of novel effective Hsp-inducers.
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamagishi
authors.forename: Saki
authors.initials: S
authors.lastname: Tokunaga
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ishihara
authors.forename: Youhei
authors.initials: Y
authors.lastname: Saito
authors.forename: Takumi
authors.initials: T
authors.lastname: Hatayama
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006360:Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000187:drug effects*; D006801:Humans; D006900:Hydroxylation; D051379:Mice; D019800:Phenol / Q000737:chemistry*; D012980:Sodium Salicylate / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D006360:Heat-Shock Proteins; D019800:Phenol; D012980:Sodium Salicylate