title: Possible involvement of HSP90-HSF1 multichaperone complex in impairment of HSP72 induction in the failing heart following myocardial infarction in rats.
abstract: It is generally accepted that an increase in the myocardial level of heat-shock protein 72 (HSP72) protects viable cardiac tissue against myocardial infarction (MI)-induced stress. However, the induction of HSP72 after exposure to heat shock (HS) is blunted in the failing rat heart following MI. The mechanisms underlying this impairment in the HSP72 induction ability of the failing heart are not yet clearly defined. In the present study, we examined the involvement in heat-shock factor 1 (HSF1), a transcription factor of HSPs, in decreased ability for HSP72 induction in the failing rat heart following MI. In the failing heart, nuclear translocation of the HSF1 after exposure to hyperthermia was markedly reduced, whereas HSF1 in the cytosolic fraction and the HSP90 chaperone complex containing HSF1, a repressor of HSF1, were increased. Treatment with an HSP90 inhibitor, 17-allylamino-17-demethoxygel-danamycin, appeared to dissociate the interaction of HSF1 with HSP90, and then induced HSP72 in the failing heart after exposure to hyperthermia. These results suggest that an increase in the multichaperone complex, especially the HSF1-HSP90 interaction, associated with attenuation of HSF1 translocation into the nucleus, was involved in the impairment of HS-induced HSP72 induction in the failing heart following MI.
authors.affiliation: Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Marunouchi
authors.forename: Masato
authors.initials: M
authors.lastname: Araki
authors.forename: Mao
authors.initials: M
authors.lastname: Murata
authors.forename: Norio
authors.initials: N
authors.lastname: Takagi
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tanonaka
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005334:Fever; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D006333:Heart Failure / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D008297:Male; D018832:Molecular Chaperones / Q000502:physiology*; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
chemical_list: D016227:Benzoquinones; D004268:DNA-Binding Proteins; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C000619709:Hsf1 protein, rat; D047029:Lactams, Macrocyclic; D018832:Molecular Chaperones; D014157:Transcription Factors; C112765:tanespimycin