title: Non-Hsp genes are essential for HSF1-mediated maintenance of whole body homeostasis.
abstract: Mammalian tissues are always exposed to diverse threats from pathological conditions and aging. Therefore, the molecular systems that protect the cells from these threats are indispensable for cell survival. A variety of diseases, including neurodegenerative diseases, cause intracellular damage and disturb homeostasis. Heat shock transcription factor 1 (HSF1) positively regulates heat shock protein (Hsp) and maintains the precise folding of proteins. Moreover, HSF1 induces the non-Hsp genes expression, and degrades damaged/misfolded protein. Recently, my colleagues and I revealed non-Hsp genes have more protective roles than Hsps at the cellular level. However, whether these protective systems are similarly important to cellular defense in each tissue is still elusive. In this study, I compared polyglutamine (polyQ) protein aggregations/inclusion development in each tissue of WT- and HSF1KO-Huntington's disease (HD) mice, and examined the expression of the eight non-Hsp HSF1 target genes that have a strong suppressive effect on polyQ protein aggregation. Of these genes, Nfatc2, Pdzk3, Cryab, Csrp2, and Prame were detected in most tissues, but the other genes were not. Surprisingly, the obvious effect of HSF1 deficiency on the expression of these five genes was detected in only heart, spleen, and stomach. In addition, polyQ protein aggregations/inclusion was not detected in any tissues of WT-HD and HSF1KO-HD mice, but higher level of pre-aggregative polyQ protein was detected in HSF1KO-HD tissues. These results indicate non-Hsp genes are indispensable for the maintenance of intracellular homeostasis in mammalian tissues, resulting in whole body homeostasis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashida
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D000076249:Heat Shock Transcription Factors; D006706:Homeostasis / Q000235:genetics*; D060588:LIM Domain Proteins / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000502:physiology*; D050778:NFATC Transcription Factors / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D010455:Peptides; D066263:Protein Aggregation, Pathological / Q000235:genetics; D017510:Protein Folding; D014157:Transcription Factors / Q000502:physiology*; D038203:alpha-Crystallin B Chain / Q000502:physiology*
chemical_list: C525420:Cryab protein, mouse; C484376:Csrp2 protein, mouse; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse; D009687:Nuclear Proteins; D010455:Peptides; D014157:Transcription Factors; D038203:alpha-Crystallin B Chain; C097188:polyglutamine