1,1,2,2-Tetrachloroethane-induced early decrease of dolichol levels in rat liver microsomes and Golgi apparatus.
Dolichols are long-chain polyprenols containing 14-22 isoprene units, present in mammalian tissues as free dolichol (Free-Dol), fatty acyl dolichyl esters (Dol-FA), and dolichyl phosphate (Dol-P). The hepatic level of Dol-P seems to be a rate-limiting factor for glycosylation processes. Previous studies from our laboratory demonstrated the susceptibility of the dolichol molecule to undergo radical attacks. Since the toxicity of 1,1,2,2-tetrachloroethane (TTCE)is dependent on the free-radical production during hepatic biotrasformation, it was of interest to determine whether this haloalkane might affect glycosylation mechanisms by changing dolichol levels and distribution in rat liver microsomes and Golgi apparatus (GA). Male Sprague-Dawley rats received a single dose of TTCE (574 mg/kg body weight) and were then sacrificed at different times (5, 15, 30, or 60 min). In the TTCE-treated rats both serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and hepatic triglycerides (TG) were significantly higher than control, while microsomal glucose 6-phosphatase (G6Pase) activity was decreased. In total microsomes Dol-P levels considered rate-limiting for the biosynthesis of the N-glycosylated proteins were significantly lower than in the control group 15 min after TTCE treatment. In normal rat liver, F1 secretory fraction of CA is 60-fold enriched in total dolichol content with respect to microsomes. In this compartment the total dolichol content, essential for the increase in membrane fluidity and permeability required for glycoprotein maturation and secretion, decreased significantly 5 min after TTCE treatment. Our results suggest that TTCE may affect dolichol functions in rat liver.
Cottalasso
D
D
Institute of General Pathology, University of Genoa, Italy. patgen@unige.it
Bellocchio
A
A
Domenicotti
C
C
Dapino
D
D
Pronzato
M A
MA
Nanni
G
G
D000818:Animals; D004286:Dolichols / Q000378:metabolism*; D004980:Ethane / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D005609:Free Radicals; D006031:Glycosylation; D006056:Golgi Apparatus / Q000187:drug effects* / Q000378:metabolism; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004286:Dolichols; D005609:Free Radicals; D006843:Hydrocarbons, Chlorinated; C015530:1,1,2,2-tetrachloroethane; D004980:Ethane