Osmoadaptation of Mammalian Cells - An Orchestrated Network of Protective Genes

In mammals, the cells of the renal medulla are physiologically exposed to interstitial osmolalities several-fold higher that found in any other tissue. Nevertheless, these cells not only have the ability to survive in this harsh environment, but also to function normally, which is critical for maintenance of systemic electrolyte and fluid homeostasis. Over the last two decades, a substantial body of evidence has accumulated, indicating that sequential and well orchestrated genomic responses are required to provide tolerance to osmotic stress. This includes the enhanced expression and action of immediate-early genes, growth arrest and DNA damage inducible genes (GADDs), genes involved in cell cycle control and apoptosis, heat shock proteins, and ultimately that of genes involved in the intracellular accumulation of nonperturbing organic osmolytes. The present review summarizes the sequence of genomic responses conferring resistance against osmotic stress. In addition, the regulatory mechanisms mediating the coordinated genomic response to osmotic stress will be highlighted.