Effects of 1,2-dichloroethane intoxication on dolichol levels and glycosyltransferase activities in rat liver microsomes and Golgi apparatus.
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.
Cottalasso
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Institute of General Pathology, University of Genoa, Italy.
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Gazzo
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Dapino
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Domenicotti
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Pronzato
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Nanni
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D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002463:Cell Membrane Permeability / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004288:Dolichol Phosphates / Q000378:metabolism; D004286:Dolichols / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects; D005025:Ethylene Dichlorides / Q000506:poisoning / Q000633:toxicity*; D005700:Galactosyltransferases / Q000378:metabolism; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism*; D006056:Golgi Apparatus / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D012799:Sialyltransferases / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D004288:Dolichol Phosphates; D004286:Dolichols; D005025:Ethylene Dichlorides; D014280:Triglycerides; C028306:dolichol monophosphate; C024565:ethylene dichloride; D016695:Glycosyltransferases; D005700:Galactosyltransferases; D012799:Sialyltransferases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase