PMID:26251235

Citation	Hayashida, N (2015) Non-Hsp genes are essential for HSF1-mediated maintenance of whole body homeostasis. Exp. Anim. 64:397-406
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.
Links	PubMed PMC4637377 Online version:10.1538/expanim.15-0023
Keywords	Animals; DNA-Binding Proteins/physiology; Female; Heat Shock Transcription Factors; Homeostasis/genetics; LIM Domain Proteins/physiology; Male; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Transgenic; Muscle Proteins/physiology; NFATC Transcription Factors/physiology; Nuclear Proteins/physiology; Peptides; Protein Aggregation, Pathological/genetics; Protein Folding; Transcription Factors/physiology; alpha-Crystallin B Chain/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:HSF1		GO:0010628: positive regulation of gene expression	ECO:0000315:		P		Figure 4 shows a significant decrease in mRNA production in the HSF1KO-HD in mice relative to the control group. This indicates that HSF1 is a positive regulator of gene expression in Nfatc2, Pdzk3, and Cryab in heart, spleen and straitium tissues.	complete CACAO 13054

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