The phenylic hydroxyl group is essential for the induction of stress response by sodium salicylate.
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.
Yamagishi
Nobuyuki
N
Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
Tokunaga
Saki
S
Ishihara
Keiichi
K
Saito
Youhei
Y
Hatayama
Takumi
T
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
D006360:Heat-Shock Proteins; D019800:Phenol; D012980:Sodium Salicylate