Bimoclomol, a heat shock protein co-inducer, acts by the prolonged activation of heat shock factor-1. Biochem Biophys Res Commun 2003 Aug 01;307(3):689-95
Date
08/02/2003Pubmed ID
12893279DOI
10.1016/s0006-291x(03)01254-3Scopus ID
2-s2.0-0042170384 98 CitationsAbstract
The novel hydroxylamine derivative, bimoclomol, has been shown previously to act as a co-inducer of several heat shock proteins (Hsp-s), enhancing the amount of these proteins produced following a heat shock compared to heat shock alone. Here we show that the co-inducing effect of bimoclomol on Hsp expression is mediated via the prolonged activation of the heat shock transcription factor (HSF-1). Bimoclomol effects are abolished in cells from mice lacking HSF-1. Moreover, bimoclomol binds to HSF-1 and induces a prolonged binding of HSF-1 to the respective DNA elements. Since HSF-1 does not bind to DNA in the absence of stress, the bimoclomol-induced extension of HSF-1/DNA interaction may contribute to the chaperone co-induction of bimoclomol observed previously. These findings indicate that bimoclomol may be of value in targeting HSF-1 so as to induce up-regulation of protective Hsp-s in a non-stressful manner and for therapeutic benefit.
Author List
Hargitai J, Lewis H, Boros I, Rácz T, Fiser A, Kurucz I, Benjamin I, Vígh L, Pénzes Z, Csermely P, Latchman DSAuthor
Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Line
Cells, Cultured
DNA-Binding Proteins
HSP70 Heat-Shock Proteins
Heat Shock Transcription Factors
Heat-Shock Proteins
Humans
Imides
Kinetics
Macromolecular Substances
Mice
Mice, Knockout
Phosphorylation
Pyridines
RNA Stability
Response Elements
Transcription Factors
