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Author

Kwon, H. Moo
Inflammation and Kidney Disorder Lab
Research Interests
  • TonEBP, Obesity, Cancer, Chronic inflammatory diseases, Brain disorder, Kidney disorders, Genomic instability

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Bidirectional regulation of tonicity-responsive enhancer binding protein in response to changes in tonicity

Cited 97 times inthomson ciCited 101 times inthomson ci
Title
Bidirectional regulation of tonicity-responsive enhancer binding protein in response to changes in tonicity
Author
Woo, SKDahl, SCHandler, JSKwon, H. Moo
Keywords
Aldose reductase; Hypertonicity-stimulated transcription; Sodium-chloride-betaine cotransporter; Sodium-myo-inositol cotransporter
Issue Date
200006
Publisher
AMER PHYSIOLOGICAL SOC
Citation
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v.278, no.6, pp.F1006 - F1012
Abstract
Tonicity-responsive enhancer binding protein (TonEBP) regulates transcription of tonicity responsive genes such as the sodium-myo-inositol cotransporter (SMIT), the sodium-chloride-betaine cotransporter (BGT1), and aldose reductase (AR). To characterize signals that activate TonEBP in Madin- Darby canine kidney (MDCK) cells, the abundance and nuclear distribution of TonEBP were studied after the osmolality of the culture medium was changed. Hypertonicity but not hyperosmolality is effective in activation of TonEBP as expected. Surprisingly, exposure to hypotonic medium leads to a dramatic downregulation of TonEBP both in abundance and nuclear distribution, indicating that under isotonic conditions, TonEBP is at a low-level activated state and can respond to both increase and decrease in tonicity. Additional experiments suggest that cellular ionic strength is the signal that initiates regulation of TonEBP. The increase in abundance of TonEBP is mediated by an increase in mRNA abundance and a parallel increase in synthesis of TonEBP. The stability of TonEBP mRNA is not affected by hypertonicity indicating that transcription plays a major role in the induction of TonEBP by hypertonicity.
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ISSN
1931-857X
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