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

Judit Hargitai, Hannah Lewis, I. Boros, Tímea Rácz, András Fiser, István Kurucz, Ivor Benjamin, L. Vígh, Zoltán Pénzes, P. Csermely, David S. Latchman

Research output: Contribution to journalArticle

98 Citations (Scopus)

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 languageEnglish
Pages (from-to)689-695
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume307
Issue number3
DOIs
Publication statusPublished - Aug 1 2003

Fingerprint

Heat-Shock Proteins
Shock
Hot Temperature
Chemical activation
DNA
Hydroxylamine
bimoclomol
Up-Regulation
Derivatives
Proteins

Keywords

  • Bimoclomol
  • Chaperones
  • HSF-1
  • Hsp47
  • Hsp70
  • Hsp90

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Bimoclomol, a heat shock protein co-inducer, acts by the prolonged activation of heat shock factor-1. / Hargitai, Judit; Lewis, Hannah; Boros, I.; Rácz, Tímea; Fiser, András; Kurucz, István; Benjamin, Ivor; Vígh, L.; Pénzes, Zoltán; Csermely, P.; Latchman, David S.

In: Biochemical and Biophysical Research Communications, Vol. 307, No. 3, 01.08.2003, p. 689-695.

Research output: Contribution to journalArticle

Hargitai, Judit ; Lewis, Hannah ; Boros, I. ; Rácz, Tímea ; Fiser, András ; Kurucz, István ; Benjamin, Ivor ; Vígh, L. ; Pénzes, Zoltán ; Csermely, P. ; Latchman, David S. / Bimoclomol, a heat shock protein co-inducer, acts by the prolonged activation of heat shock factor-1. In: Biochemical and Biophysical Research Communications. 2003 ; Vol. 307, No. 3. pp. 689-695.
@article{0d3034f28825449bb07deddb3dda571f,
title = "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.",
keywords = "Bimoclomol, Chaperones, HSF-1, Hsp47, Hsp70, Hsp90",
author = "Judit Hargitai and Hannah Lewis and I. Boros and T{\'i}mea R{\'a}cz and Andr{\'a}s Fiser and Istv{\'a}n Kurucz and Ivor Benjamin and L. V{\'i}gh and Zolt{\'a}n P{\'e}nzes and P. Csermely and Latchman, {David S.}",
year = "2003",
month = "8",
day = "1",
doi = "10.1016/S0006-291X(03)01254-3",
language = "English",
volume = "307",
pages = "689--695",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Bimoclomol, a heat shock protein co-inducer, acts by the prolonged activation of heat shock factor-1

AU - Hargitai, Judit

AU - Lewis, Hannah

AU - Boros, I.

AU - Rácz, Tímea

AU - Fiser, András

AU - Kurucz, István

AU - Benjamin, Ivor

AU - Vígh, L.

AU - Pénzes, Zoltán

AU - Csermely, P.

AU - Latchman, David S.

PY - 2003/8/1

Y1 - 2003/8/1

N2 - 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.

AB - 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.

KW - Bimoclomol

KW - Chaperones

KW - HSF-1

KW - Hsp47

KW - Hsp70

KW - Hsp90

UR - http://www.scopus.com/inward/record.url?scp=0042170384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042170384&partnerID=8YFLogxK

U2 - 10.1016/S0006-291X(03)01254-3

DO - 10.1016/S0006-291X(03)01254-3

M3 - Article

C2 - 12893279

AN - SCOPUS:0042170384

VL - 307

SP - 689

EP - 695

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 3

ER -