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 administration (6 g/kg body weight) selectively and rapidly affects the intracellular system of protein glycosylation at the level of the Golgi apparatus. Dolichols are important membrane components, and dolichyl phosphate is a glycosyl sugar carrier for N-glycosylation of proteins in endoplasmic reticulum and is considered rate-limiting for this process. 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 microsomal 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 F1 (-70% at 6 hr). Ethanol treatment of isolated hepatocytes led to a significant reduction of the de novo synthesis of both dolichyl phosphate and free dolichol. Moreover, in vitro experiments have demonstrated that pro-oxidant agents lead to a significant decrease of both free dolichol and dolichyl phosphate. Our results suggest that acute ethanol administration induces a marked decrease of dolichols, probably by increasing the degradation and impairing the biosynthetic pathway of these molecules.
Cottalasso
D
D
Institute of General Pathology, University of Genoa, Italy.
Bellocchio
A
A
Pronzato
M A
MA
Domenicotti
C
C
Traverso
N
N
Gianelli
M V
MV
Marinari
U M
UM
Nanni
G
G
D000818:Animals; D004286:Dolichols / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006031:Glycosylation / Q000187:drug effects; D006056:Golgi Apparatus / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004286:Dolichols; D000431:Ethanol