Abstract
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.
Original language | English (US) |
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Pages (from-to) | 689-695 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 307 |
Issue number | 3 |
DOIs | |
State | Published - Aug 1 2003 |
Externally published | Yes |
Keywords
- Bimoclomol
- Chaperones
- HSF-1
- Hsp47
- Hsp70
- Hsp90
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology