TonEBP/NFAT5 stimulates transcription of HSP70 in response to hypertonicity
Cited 124 times inCited 0 times in
- TonEBP/NFAT5 stimulates transcription of HSP70 in response to hypertonicity
- Woo, SK; Lee, SD; Na, KY; Park, WK; Kwon, H. Moo
- ENHANCER-BINDING PROTEIN; HIGH UREA CONCENTRATIONS; CANINE KIDNEY-CELLS; GENE-TRANSCRIPTION; EPITHELIAL-CELLS; MEDULLARY CELLS; OSMOTIC-STRESS; RAT-KIDNEY; MDCK CELLS; TONICITY
- Issue Date
- AMER SOC MICROBIOLOGY
- MOLECULAR AND CELLULAR BIOLOGY, v.22, no.16, pp.5753 - 5760
- While hyperosmolality of the kidney medulla is essential for urinary concentration, it imposes a great deal of stress. Cells in the renal medulla adapt to the stress of hypertonicity (hyperosmotic salt) by accumulating organic osmolytes. Tonicity-responsive enhancer (TonE) binding protein (TonEBP) (or NFAT5) stimulates transcription of transporters and a synthetic enzyme for the cellular accumulation of organic osmolytes. We found that dominant-negative TonEBP reduced expression of HSP70 as well as the transporters and enzyme. Near the major histocompatibility complex class III locus, there are three HSP70 genes named HSP70-1, HSP70-2, and HSC70t. While HSP70-1 and HSP70-2 were heat inducible, only HSP70-2 was induced by hypertonicity. In the 5' flanking region of the HSP70-2 gene, there are three sites for TonEBP binding. In cells transfected with a reporter plasmid containing this region, expression of luciferase was markedly stimulated in response to hypertonicity. Coexpression of the dominant-negative TonEBP reduced the luciferase expression. Mutating all three sites in the reporter plasmid led to a complete loss of induction by hypertonicity. Thus, TonEBP rather than heat shock factor stimulates transcription of the HSP70-2 gene in response to hypertonicity. We conclude that TonEBP is a master regulator of the renal medulla for cellular protection against high osmolality via organic osmolytes and molecular chaperones.
- ; Go to Link
- Appears in Collections:
- BME_Journal Papers
- Files in This Item:
can give you direct access to the published full text of this article. (UNISTARs only)
Show full item record
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.