dolichols and Inflammation

Inflammation and glucocorticoids stimulate hepatic glycoprotein synthesis, resulting in an increased secretion of serum glycoproteins. We now present evidence that the synthesis of dolichol and dolichol phosphate from mevalonate is increased in hepatocytes from inflamed rats. Also, in inflamed rats, the levels of dolichol and dolichol phosphate are increased in liver homogenates and microsomes. Dexamethasone treatment of the cells, however, does not increase the synthesis of dolichol and dolichol phosphate from mevalonate. The results suggest that the inflammation-induced dolichol-linked saccharide and glycoprotein synthesis is possibly mediated through an increase in the level of dolichol and dolichol phosphate in the liver. Since dexamethasone treatment does not increase the synthesis of dolichol and dolichol phosphate, its action on glycoprotein synthesis appears to be different and to affect the induction of enzymes in mannosyl phosphoryl dolichol- and dolichol-linked oligosaccharide synthesis.

Topics: Animals; Chromatography, High Pressure Liquid; Dexamethasone; Dolichol Phosphates; Dolichols; Inflammation; Liver; Male; Mevalonic Acid; Microsomes, Liver; Polyisoprenyl Phosphates; Rats; Rats, Inbred Strains; Turpentine

Inflammation was induced in rats by the subcutaneous injection of turpentine. Microsomes were prepared from the livers between 2 and 72 h after injection. Mannose and glucose incorporation into mannosyl and glucosyl dolichyl monophosphate was increased 2-fold over saline-injected controls 24 h after induction of inflammation. Synthesis of glycosylated dolichyl pyrophosphoryl oligosaccharides was also increased compared to controls. Extraction and assay of dolichol monophosphate from inflamed and control rat liver microsomes indicated that the endogenous levels of the lipid were elevated in the inflamed state. CTP-dependent phosphorylation of endogenous dolichol was also found to increase in microsomes from inflamed rats 24 h after injection of turpentine. When exogenous dolichol was added to the microsomal system an increase in phosphorylation was observed as early as 6 h after turpentine injection. Furthermore, the increase appeared to be biphasic, there being two peaks of elevated activity at 12 and 36-48 h after induction of inflammation. The earlier peak was the greater of the two. The results suggest that the increase in glycosylation of dolichol derivatives was due to greater amounts of endogenous dolichol monophosphate. The increase in dolichol monophosphate was itself due to greater availability of dolichol and an increase in the levels of CTP-dependent dolichol kinase.

Topics: Animals; Diterpenes; Dolichol Phosphates; Dolichols; Glycosides; Hexosyltransferases; Inflammation; Kinetics; Male; Microsomes, Liver; Phosphorylation; Phosphotransferases; Phosphotransferases (Alcohol Group Acceptor); Rats; Turpentine