T. Pradhap, M. Ashokan and Manoj G. Tyagi
The transcription factor, tonicity-responsive enhan cer binding protein (TonEBP) plays a key role in th e accumulation of organic osmolytes by stimulating ge ne expression of membrane transporters (sodium-inositol cotransporter and sodium-chloride- betaine cotransporter) and a biosynthetic enzyme (aldose reductase) that catalyzes production of sorb itol from glucose. Thus, TonEBP plays a key regulatory role in protecting the renal medulla fro m the deadly stress of hypertonicity. Although TonEBP plays a key role in hypertonicity induced st imulation of gene transcription in the renal medull a and T cells, TonEBP is active under isotonic cond itions. These wide-ranging transcriptional targets delineate TonEBP as a critical element of osmosenso ry signal transduction in cells of the renal medulla. In this study, we ascertained the role of TonEBP on the heart rate in conjunction with pituit ary hormone vasopressin and with vasoconstrictor endoth elin antagonist, BQ-123. We also studied the effects of Ton EBP modulators on glucose and ketone levels in the urine and on the blood potassium and sodium levels. We utilized, doxorubicin (Dox) an d isosorbide dinitrate to modulate the levels of TonEBP endogenously.
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