Navarro Paola, Chiong Mario, Volkwein Karen, Moraga Francisco, Ocaranza María Paz, Jalil Jorge E, Lim Sun Woo, Kim Jeong-Ah, Kwon H Moo, Lavandero Sergio
Centro FONDAP de Estudios Moleculares de la Célula, Universidad de Chile, Olivos 1007, Santiago 838-0492, Chile.
Biochem Biophys Res Commun. 2008 Jul 25;372(2):326-30. doi: 10.1016/j.bbrc.2008.05.067. Epub 2008 May 23.
Changes in cardiac osmolarity occur in myocardial infarction. Osmoregulatory mechanisms may, therefore, play a crucial role in cardiomyocyte survival. Tonicity-responsive enhancer binding protein (TonEBP) is a key transcription factor participating in the adaptation of cells to increases in tonicity. However, it is unknown whether cardiac TonEBP is activated by tonicity. Hypertonicity activated transcriptional activity of TonEBP, increased the amounts of both TonEBP mRNA and protein, and induced both the mRNA and protein of TonEBP target genes (aldose reductase and heat shock protein-70). Hypotonicity decreased the amount of TonEBP protein indicating bidirectional osmoregulation of this transcription factor. Adenoviral expression of a dominant negative TonEBP suppressed the hypertonicity-dependent increase of aldose reductase protein. These results indicated that TonEBP controls osmoregulatory mechanisms in cardiomyocytes.
心肌梗死时心脏渗透压会发生变化。因此,渗透调节机制可能在心肌细胞存活中起关键作用。张力反应增强子结合蛋白(TonEBP)是参与细胞适应张力增加的关键转录因子。然而,尚不清楚心脏中的TonEBP是否被张力激活。高渗激活了TonEBP的转录活性,增加了TonEBP mRNA和蛋白质的量,并诱导了TonEBP靶基因(醛糖还原酶和热休克蛋白70)的mRNA和蛋白质表达。低渗降低了TonEBP蛋白的量,表明该转录因子存在双向渗透调节。显性负性TonEBP的腺病毒表达抑制了醛糖还原酶蛋白的高渗依赖性增加。这些结果表明,TonEBP控制心肌细胞中的渗透调节机制。