Abstract

Abstract Evolutionarily, adaptation to hyperosmotic stress through accumulation of osmotically active organic solutes (organic osmolytes) is a highly conserved mechanism. Hyperosmotic accumulation of organic osmolytes is transcriptionally regulated: e.g., betaine in bacteria (e.g., Escherichia coli), glycerol in yeast (e.g., Saccharomyces cerevisiae), betaine in plants (e.g., Spinacea oleracea L.) and sorbitol, betaine, and inositol in cells of the mammalian renal medulla. Renal medullary cells, among mammalian cells, are uniquely exposed to hyperosmotic stress; in these cells, hyperosmotic stress results in accumulation of sorbitol as one of the predominant osmolytes. Sorbitol accumulates due to a rise in the synthesis rate of aldose reductase (AR), which catalyzes the conversion of glucose to sorbitol. Hyperosmotic stress increases transcription of the AR gene which leads to a rise in AR mRNA levels. In cloning and characterizing the rabbit AR gene, the first evidence of a eukaryotic osmotic response el...

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