Cottalasso D, Fontana L, Gazzo P, Dapino D, Domenicotti C, Pronzato M A, Nanni G
Institute of General Pathology, University of Genoa, Italy.
Toxicology. 1995 Dec 15;104(1-3):63-71. doi: 10.1016/0300-483x(95)03130-8.
Rat intoxication with a single dose of 1,2-dichloroethane (DCE) (50 microliters/100 g b.w) is able to induce a significant modification of protein glycosylation in the liver endoplasmic reticulum and Golgi apparatus. HPLC analysis shows that within 5-60 min after DCE-intoxication, the levels of total dolichol, free dolichol and dolichyl phosphate strongly decreased in the microsomes and Golgi apparatus. Particularly in total microsomes, dolichyl phosphate, which is rate-limiting for the biosynthesis of the N-linked oligosaccharide chains, drops to values significantly lower than in the control group 15 min after DCE poisoning. In the Golgi apparatus, the total dolichol, essential to enhance the fluidity and permeability of these membranes, early and significantly decreases already 5 min after DCE poisoning. Moreover, in the Golgi apparatus galactosyl- and sialyltransferase activities, the main enzymatic activities of terminal protein glycosylation, are significantly reduced, as measured 15 min after DCE intoxication. These data suggest that the impairment of glycoprotein synthesis, maturation and secretion may be involved in the pathogenesis of liver injury induced by acute DCE-intoxication.
单次给予大鼠1,2 - 二氯乙烷(DCE)(50微升/100克体重)可导致肝脏内质网和高尔基体中蛋白质糖基化的显著改变。高效液相色谱分析表明,DCE中毒后5 - 60分钟内,微粒体和高尔基体中总多萜醇、游离多萜醇和多萜醇磷酸酯的水平显著下降。特别是在总微粒体中,作为N - 连接寡糖链生物合成限速步骤的多萜醇磷酸酯,在DCE中毒15分钟后降至明显低于对照组的值。在高尔基体中,对于增强这些膜的流动性和通透性至关重要的总多萜醇,在DCE中毒5分钟后就早早显著降低。此外,在高尔基体中,作为末端蛋白质糖基化主要酶活性的半乳糖基转移酶和唾液酸转移酶活性,在DCE中毒15分钟后测定时显著降低。这些数据表明,糖蛋白合成、成熟和分泌的受损可能参与了急性DCE中毒所致肝损伤的发病机制。