REGULATION OF ALDOSE REDUCTASE EXPRESSION IN RAT ASTROCYTES IN CULTURE

Aldose reductase (AR) is known to be responsible for many side effects of diabetes. In the present work, we studied the effects of various e xtracellular signals on the regulation of the expression of AR in astr ocytes in culture, by determining its enzymatic activity or its mRNA l evel. We found that basic fibroblast growth factor (bFGF), acidic fibr oblast growth factor (aFGF), epidermal growth factor (EGF), and hypert onic NaCl were able to increase the expression of AR in astrocytes. A superinduction was found when bFGF was combined with hypertonicity. We also observed that AR activity was independent of glucose concentrati on in the culture medium. However, when the concentration of glucose i n the culture medium was under 1 g/l, bFGF did not increase the activi ty of AR. Thus, when glucose is depleted, the regulation of AR express ion by bFGF does not operate. In addition, AR does not seem to be invo lved in control of astrocyte proliferation, in contrast to the effects reported on other cell types. These results indicate that AR is expre ssed in astrocytes and that its expression is upregulated by hypertoni city but also by FGFs and EGF. This suggests that in these cells, AR e licits some regulatory functions. (C) 1997 Wiley-Liss, Inc.