title: Induction of heat shock proteins by hyperthermia and noise overstimulation in hsf1 -/- mice.
abstract: Diverse cellular and environmental stresses can activate the heat shock response, an evolutionarily conserved mechanism to protect proteins from denaturation. Stressors activate heat shock transcription factor 1 (HSF1), which binds to heat shock elements in the genes for heat shock proteins, leading to rapid induction of these important molecular chaperones. Both heat and noise stress are known to activate the heat shock response in the cochlea and protect it from subsequent noise trauma. However, the contribution of HSF1 to induction of heat shock proteins following noise trauma has not been investigated at the molecular level. We evaluated the role of HSF1 in the cochlea following noise stress by examining induction of heat shock proteins in Hsf1                         (                            +/-                         ) control and Hsf1                         (                            -/-                         ) mice. Heat stress rapidly induced expression of Hsp25, Hsp47, Hsp70.1, Hsp70.3, Hsp84, Hsp86, and Hsp110 in the cochleae of wild-type and Hsf1                         (                            +/-                         ) mice, but not in Hsf1                         (                            -/-                         ) mice, confirming the essential role of HSF1 in mediating the heat shock response. Exposure to broadband noise (2-20 kHz) at 106 dB SPL for 2 h produced partial hearing loss. Maximal induction of heat shock proteins occurred 4 h after the noise. In comparison to heat stress, noise stress resulted in lower induced levels of Hsp25, Hsp70.1, Hsp70.3, Hsp86, and Hsp110 in Hsf1                         (                            +/-                         ) mice. Induction of these heat shock proteins was attenuated, but not completely eliminated, in Hsf1                         (                            -/-                         ) mice. These same noise exposure conditions induced genes for several immediate early transcription factors and maximum induction occurred earlier than for heat shock proteins. Thus, additional signaling pathways and transcriptional regulators that are activated by noise probably contribute to induction of heat shock proteins in the cochlea.
authors.affiliation: Department of Otolaryngology/Head Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109-5648, USA.
authors.forename: Tzy-Wen
authors.initials: TW
authors.lastname: Gong
authors.forename: Damon A
authors.initials: DA
authors.lastname: Fairfield
authors.forename: Lynne
authors.initials: L
authors.lastname: Fullarton
authors.forename: David F
authors.initials: DF
authors.lastname: Dolan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Altschuler
authors.forename: David C
authors.initials: DC
authors.lastname: Kohrman
authors.forename: Margaret I
authors.initials: MI
authors.lastname: Lomax
mesh_terms: D000818:Animals; D003051:Cochlea / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005334:Fever / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D015870:Gene Expression / Q000502:physiology; D017781:Genes, Immediate-Early / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006317:Hearing Loss, Noise-Induced / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009622:Noise / Q000009:adverse effects; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; C490017:Hsf1 protein, mouse; C107835:Hspca protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D014157:Transcription Factors