EFFECT OF ETHANOL ADMINISTRATION ON THE LEVEL OF DOLICHOL IN RAT-LIVER MICROSOMES AND GOLGI-APPARATUS

Data obtained in our laboratory had suggested that acute ethanol admin istration (6 g/kg body weight) selectively and rapidly affects the int racellular system of protein glycosylation at the level of the Golgi a pparatus. Dolichols are important membrane components, and dolichyl ph osphate is a glycosyl sugar carrier for N-glycosylation of proteins in endoplasmic reticulum and is considered rate-limiting for this proces s. In this study, modifications in the concentration and distribution of liver microsomal dolichols after acute ethanol administration were investigated. Between 3 and 24 hr after ethanol administration, the mi crosomal dolichyl phosphate concentration was significantly lower than in control animals. The highest reduction was observed at 12 hr (-52% ). An earlier and more marked reduction of total dolichol was observed in the Golgi apparatus, and, in particular, in the secretory fraction F-1 (-70% at 6 hr). Ethanol treatment of isolated hepatocytes led to a significant reduction of the de novo synthesis of both dolichyl phos phate and free dolichol. Moreover, in vitro experiments have demonstra ted that pro-oxidant agents lead to a significant decrease of both fre e dolichol and dolichyl phosphate. Our results suggest that acute etha nol administration induces a marked decrease of dolichols, probably by increasing the degradation and impairing the biosynthetic pathway of these molecules.