ALDOSE REDUCTASE MESSENGER-RNA EXPRESSION AND ITS ACTIVITY ARE INDUCED BY GLUCOSE IN FETAL-RAT AORTIC SMOOTH-MUSCLE (A10) CELLS

The induction of aldose reductase (AR) mRNA expression and its activity by glucose were investigated in fetal rat aortic smooth muscle (A10) cells. The increase in the expression of AR mRNA was observed at 6 h, and reached a maximum (2.3 fold) at 12 h after exposure to 80 mM glucose. On the other hand, increase in AR activity was observed at 12 h and reached a maximum (2 fold) at 48 h after exposure to 80 mM glucose. AR mRNA levels as well as its activity increased almost linearly in a concentration dependent manner up to 80 mM. Although not significant, there was a consistent increase in AR mRNA level and its activity at 23.75 mM glucose. There was a good correlation between AR mRNA level and AR activity. In the presence of 1-mu-g/ml actinomycin D, the increase in the expression of AR mRNA level by glucose was almost completely abolished, suggesting its transcriptional regulation by glucose. Other osmolytes were also effective in inducing AR mRNA expression as well as its activity at 80 mOsm/kg. Therefore, the increase in AR mRNA level and its activity by glucose in A10 cells may be a response to the increase in osmolarity.