EFFECTS OF ACETALDEHYDE ON GLUCOSE-6-PHOSPHATE-DEHYDROGENASE ACTIVITYAND MESSENGER-RNA LEVELS IN PRIMARY RAT HEPATOCYTES IN CULTURE

Ethanol has been shown to induce the activity of glucose-6-phosphate d ehydrogenase (G6PDH). To clarify the mechanism behind this induction, we examined the role of acetaldehyde (AA), the first product of ethano l metabolism. In primary adult rat hepatocytes maintained in chemicall y defined medium, we examined the effect of AA on G6PDH activity, mRNA levels and lipid synthesis. We observe a 40% increase in G6PDH activi ty and a similar increase in mRNA levels, following exposure to 100 mu M AA. The increase in activity was found to be maximal at 24 h while m RNA levels increased over controls as early as 3 h. The induction in G 6PDH by AA was found to occur at lower concentrations and earlier time points than those reported using ethanol. The role of insulin, a know n inducer of G6PDH activity was studied alone and in combination with AA on both G6PDH activity and mRNA levels as well as lipid biosynthesi s. Insulin (300 ng/ml) was found to increase G6PDH activity, mRNA leve ls and [C-14]-acetate incorporation into lipid. It was also shown to h ave an additive effect with AA on G6PDH activity suggesting their acti ons are mediated via different mechanistic pathways. No change in [C-1 4]-acetate incorporation into lipid, however, was observed with acetal dehyde alone.