Renal medullary organic osmolytes

Abstract

Sorbitol, inositol, GPC, and betaine are the predominant organic osmolytes in renal medullary cells. They protect the cells from harmful effects of the high interstitial NaCl and urea concentrations that occur normally in the renal medulla with operation of the urinary concentrating mechanism. Their levels correlate with extracellular NaCl concentration and, in the case of GPC, also with urea. Sorbitol is synthesized from glucose in a reaction catalyzed by aldose reductase. Inositol and betaine are transported into the cell. Glycerophosphorylcholine synthesis is dependent on choline. The transcription of aldose reductase and the transport of betaine and inositol are regulated, dependent on the degree of hypertonicity. Normal organic osmolyte regulation contributes to the survival and growth of medullary cells in their hyperosmolal environment, and defective regulation can damage them.

Cells adapted to high NaCl have many DNA breaks and impaired DNA repair both in cell culture and in vivo

“…The known protective responses include accumulation of organic osmolytes (30), up-regulation of heat shock proteins (12,13), and activation of Na͞K ATPase (12). In cell culture, high NaCl causes DNA damage (8,9), but also induces transient cell cycle arrest (14,16,18), which was believed to provide time for repair of the DNA.…”

“…The classical view is that hypertonicity can be compensated for by maintaining normal cell volume and intracellular ion composition by replacement of inorganic ions with compatible osmolites (30), thus ensuring biochemical and metabolic stability. Now, we find that those compensations do not prevent DNA damage or preserve the DNA damage response in adapted cells.…”

Pax2 expression occurs in renal medullary epithelial cells in vivo and in cell culture, is osmoregulated, and promotes osmotic tolerance

“…The high levels of NaCl and urea present in the renal inner medulla can cause apoptosis (4), yet the inner medullary cells evidently have protective mechanisms that allow them to survive and function. One such mechanism is that a high NaCl level increases transcription, resulting in a greater abundance of proteins that protect the cells from osmotic stress, including those involved in the accumulation of intracellular organic osmolytes (5) and heat shock proteins (6).…”

Synechococcus sp. PCC7942 Transformed with Escherichia coli bet Genes Produces Glycine Betaine from Choline and Acquires Resistance to Salt Stress

“…Cyanobacteria that are able to grow in high-salt-concentration environments maintain their cell turgor by accumulation of potassium ions and by the synthesis and accumulation of low mo1 wt organic osmoprotectants. Thus, freshwater cyanobacteria accumulate disaccharides and glucosylglycerol in response to osmotic stress, whereas halotolerant forms accumulate Gly betaine (Blumwald et al, 1983;Mackay et al, 1984;Reed et al, 1986 accumulated by a wide range of organisms including bacteria, higher plants, and animals (Galinski and Truper, 1982;Csonka and Hanson, 1991;Garcia-Perez and Burg, 1991).…”