Bimoclomol, a heat shock protein co-inducer, acts by the prolonged activation of heat shock factor-1.

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.

• Authors: Judit Hargitai, Hannah Lewis, Imre Boros, Tímea Rácz, András Fiser, István Kurucz, Ivor Benjamin, László Vígh, Zoltán Pénzes, Péter Csermely, David S Latchman
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 307 Issue 3 Pg. 689-95 (Aug 01 2003) ISSN: 0006-291X [Print] United States
• PMID: 12893279 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• HSP70 Heat-Shock Proteins
• Heat Shock Transcription Factors
• Heat-Shock Proteins
• Imides
• Macromolecular Substances
• Pyridines
• Transcription Factors
• bimoclomol

Topics

• Animals
• Cell Line
• Cells, Cultured
• DNA-Binding Proteins (drug effects, genetics, metabolism)
• HSP70 Heat-Shock Proteins (genetics, metabolism)
• Heat Shock Transcription Factors
• Heat-Shock Proteins (biosynthesis)
• Humans
• Imides (metabolism, pharmacology)
• Kinetics
• Macromolecular Substances
• Mice
• Mice, Knockout
• Phosphorylation
• Pyridines (metabolism, pharmacology)
• RNA Stability
• Response Elements
• Transcription Factors