EFFECTS OF GALACTOSE FEEDING ON ALDOSE REDUCTASE GENE-EXPRESSION

Aldose reductase (AR) is implicated in the pathogenesis of the diabeti c complications and osmotic cataract. AR has been identified as an osm oregulatory protein, at least in the renal medulla. An outstanding que stion relates to the response of AR gene expression to diet-induced ga lactosemia in extrarenal tissues. This paper shows that AR gene expres sion in different tissues is regulated by a complex multifactorial mec hanism. Galactose feeding in the rat is associated with a complex and, on occasions, multiphasic pattern of changes in AR mRNA levels in kid ney, testis, skeletal muscle, and brain. These changes are not in sync hrony with the temporal sequence of changes in tissue galactitol, gala ctose, and myoinositol concentrations. Moreover, galactose feeding res ults in changes in tissue AR activities that are not related, temporal ly or quantitatively, to the alterations in tissue AR mRNA or galactit ol levels. It is concluded that AR gene expression and tissue AR activ ities are regulated by mechanisms that are not purely dependent on non specific alterations in intracellular metabolite concentrations. This conclusion is supported by the finding that chronic xylose feeding, de spite being associated with intracellular xylitol accumulation, does n ot result in alterations in AR mRNA levels, at least in the kidney.