Regulation of TonEBP transcriptional activator in MDCK cells following changes in ambient tonicity.
In response to ambient hypertonicity, TonEBP (tonicity-responsive enhancer binding protein) stimulates certain genes including those encoding cytokines, transporters for organic solutes, and a molecular chaperone. TonEBP is regulated in a bidirectional manner, upregulated by an increase in ambient tonicity while downregulated by a decrease. To investigate the role of intracellular ionic strength in the activity of TonEBP, we subjected Madin-Darby canine kidney cells to a variety of conditions. Electron microprobe analysis was performed to measure intracellular electrolytes. Under conditions in which changes in cell volume were similar, TonEBP activity correlated with the intracellular ionic strength regardless of the external tonicity. On the other hand, inhibition of the Na+/K+-ATPase and high external K+ concentration led to a decreased activity of TonEBP despite a marked increase in the intracellular ionic strength. Because isotonic swelling is known to occur under these conditions, these data suggest that dilution of the cytoplasmic constituents inhibits the activity of TonEBP. We conclude that intracellular ionic strength and water content are major factors that determine the activity of TonEBP.
Neuhofer
Wolfgang
W
Physiologisches Institut der Universität München, D-80336 Münich, Germany.
Woo
Seung Kyoon
SK
Na
Ki Young
KY
Grunbein
Rita
R
Park
Won Kun
WK
Nahm
Ohnn
O
Beck
Franz-X
FX
Kwon
H Moo
HM
D000818:Animals; D001622:Betaine / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006982:Hypertonic Solutions / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology*
D004791:Enzyme Inhibitors; D006982:Hypertonic Solutions; D012462:Saline Solution, Hypertonic; D015534:Trans-Activators; D001622:Betaine; D010042:Ouabain; D011189:Potassium Chloride