title: Activation of heat-shock factor by stretch-activated channels in rat hearts.
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.
authors.affiliation: Texas A&M University, Department of Veterinary Physiology and Pharmacology, College Station, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: J S
authors.initials: JS
authors.lastname: Wasser
authors.forename: R N
authors.initials: RN
authors.lastname: Cornelussen
authors.forename: A A
authors.initials: AA
authors.lastname: Knowlton
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005682:Gadolinium / Q000494:pharmacology; D050884:HSP72 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013314:Stress, Mechanical; D014157:Transcription Factors; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004268:DNA-Binding Proteins; D050884:HSP72 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C000619709:Hsf1 protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors; D005682:Gadolinium; D004110:Diltiazem