Heat-shock factor-1, steroid hormones, and regulation of heat-shock protein expression in the heart

Anne A Knowlton, Limin Sun

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Heat-shock proteins (HSPs) are an important family of endogenous, protective proteins. Overexpression of HSPs is protective against cardiac injury. Previously, we observed that dexamethasone activated heat-shock factor-1 (HSF-1) and induced a 60% increase in HSP72 in adult cardiac myocytes. The mechanism responsible for this effect of dexamethasone is unknown. Because HSP90 is known to bind the intracellular hormone receptors, we postulated that the interaction between HSP90, the receptors, and HSF was an important element in activation of HSF-1 by hormones. We hypothesized that there is an equilibrium between HSP90 and the various receptors/enzymes that it binds and that alteration in levels of certain hormones will alter the intracellular distribution of HSP90 and activate HSF-1. We report that, in adult cardiac myocytes, HSF-1 coimmunoprecipitates with HSP90. HSP90 redistributes in cardiac myocytes after treatment with 17β-estradiol or progesterone. Estrogen and progesterone activate HSF-1 in adult male isolated cardiac myocytes, and this is followed by an increase in HSP72 protein. Testosterone had no effect on HSP levels; however, no androgen receptor was found in cardiac myocytes; therefore, testosterone would not be expected to effect binding of HSP90 to HSF. Geldanamycin, which inactivates HSP90 and prevents it from binding to receptors, activates HSF-1 and stimulates HSP72 synthesis. Activation of HSF-1 by steroid hormones, resulting from a change in the interaction of HSP90 and HSF-1, represents a novel pathway for regulating expression of HSPs. These findings may explain some of the gender differences in cardiovascular disease.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number1 49-1
StatePublished - 2001
Externally publishedYes

Keywords

  • Estrogen
  • Geldanamycin
  • Heat-shock protein 70
  • Heat-shock protein 90
  • Progesterone
  • Testosterone

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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