Induction of the enzyme aldose reductase in a lens epithelial cell line from a transgenic mouse

Abstract

A lens epithelial cell line established from a transgenic mouse synthesizes high levels of the enzyme aldose reductase which converts sugars to polyols. This enzyme has been implicated in the formation of sugar cataracts in animals and with diabetic complications in man. The mouse aldose reductase has been characterized and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis has an apparent molecular mass of 38,000, similar to the enzyme in rat and man. The cellular enzyme is inhibited by two aldose reductase inhibitors: Sorbinil (IC50 = 1.8 X 10(-7) M) and Alcon 1576 (IC50 = 7.8 X 10(-8) M). The amount and the specific activity of the aldose reductase can be further increased in the cells by raising the osmolarity of the medium to 500 mOSM. Although the amount of aldose reductase is increased approximately sevenfold under these conditions, alpha-crystallin, one of the main lens specific proteins, remained at about the same concentration. No detectable increase in sorbitol was found within the cells, in contrast to published reports on renal cells in which this polyol increases under similar hyperosmotic conditions; however, in the lens cells there was a five-fold increase in the inositol content, suggesting that this polyol rather than sorbitol may be used to compensate for some of the changes in the osmolarity. The induction of the enzyme aldose reductase without the apparent accumulation of its product suggests a complex mechanism for osmoregulation in the lens cells.