Osmotically-induced genes are controlled by the transcription factor TonEBP in cultured cardiomyocytes.

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.

Reactive oxygen species inhibit hyposmotic stress-dependent volume regulation in cultured rat cardiomyocytes.

Cells have developed compensatory mechanisms to restore cell volume, and the ability to resist osmotic swelling or shrinkage parallels their resistance to necrosis or apoptosis. There are several mechanisms by which cells adapt to hyposmotic stress including that of regulatory volume decrease. In ischemia and reperfusion, cardiomyocytes are exposed to hyposmotic stress, but little is known as to how their volume is controlled. Exposure of cultured neonatal rat cardiomyocytes to hyposmotic media induced a rapid swelling without any compensatory regulatory volume decrease. The hyposmotic stress increased the production of reactive oxygen species, mainly through NADPH oxidase. Adenoviral overexpression of catalase inhibited the hyposmosis-dependent OH(*) production, induced the regulatory volume decrease mechanism, and prevented cell death. These results suggest that hyposmotic stress of cardiomyocytes stimulates production of reactive oxygen species which are closely linked to volume regulation and cell death.