Activation of heat-shock factor by stretch-activated channels in rat hearts

Jiang Chang, Jeremy S. Wasser, Richard N M Cornelussen, Anne A Knowlton

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Background - Previously, we have observed that the isolated, erythrocyte-perfused rabbit heart has increased levels of heat-shock protein (HSP) 72 after a mild mechanical stress. We hypothesized that stretch-activated ion channels (SACs) mediated this increase. Methods and Results - To test this hypothesis, we subjected isolated, perfused rat hearts to mechanical stretch. Gel mobility shift assay showed that heat-shock factor (HSF) was activated in hearts with mechanical stretch, but not in controls. Supershift experiments demonstrated that HSF1 was the transcription factor. Northern blots revealed the concomitant increase in HSP72 mRNA in stretched rat hearts. In a separate set of experiments, gadolinium, an inhibitor of SACs, was added to the perfusate. Gadolinium inhibited the activation of HSF and decreased HSP72 mRNA level. Because gadolinium can inhibit both SACs and L-type calcium channels, we perfused a group of hearts with diltiazem, a specific L-type calcium channel blocker, to eliminate the involvement of L-type calcium channels. Diltiazem failed to inhibit the activation of HSF. Conclusions - Stretch in the rat heart results in activation of HSF1 and an increase in HSP72 mRNA through SACs. This represents a novel mechanism of HSF activation and may be an important cardiac signaling pathway for hemodynamic stress.

Original languageEnglish (US)
Pages (from-to)209-214
Number of pages6
JournalCirculation
Volume104
Issue number2
StatePublished - Jul 10 2001
Externally publishedYes

Keywords

  • Calcium
  • Ion channels
  • Proteins
  • Stretch

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Chang, J., Wasser, J. S., Cornelussen, R. N. M., & Knowlton, A. A. (2001). Activation of heat-shock factor by stretch-activated channels in rat hearts. Circulation, 104(2), 209-214.