Dolichol and retinol content of rat liver sinusoidal cells after chronic monensin treatment.
Aim of this study was to ascertain whether an impairment of communication between parenchymal and non-parenchymal liver cells involves vitamin A intercellular transport. The following approach was adopted: liver cells were isolated from rats treated chronically with the hydrophobic ionophore monensin i.p. for 3, 5, and 7 weeks and their retinol and dolichol content was assessed. Monensin, which alters membrane flow, was used because it had previously been reported to induce liver steatosis, cholestasis and glycogenolysis after acute treatment and, by preliminary morphological examination, to impair vitamin A transport between stellate cells and hepatocytes. Dolichol was chosen as a biochemical marker because it is a membrane lipid that modulates the fluidity and permeability of the membranes that retinol must cross. After monensin treatment, a load of vitamin A was given to rats three days before sacrifice, to ascertain whether its uptake by sinusoidal liver cells was altered. The main result was a dolichol decrease in hepatocytes and in the Ito-1 subfraction. In this latter, monensin induced a decrease in dolichol content only after vitamin A load. Moreover, while the hepatocytes were able to take up a load of vitamin A normally, the Ito-1 subfraction was no longer able to store retinol. Therefore the polarised transport of retinol between hepatocytes and stellate cells seemed impaired. The behaviour of sinusoidal endothelial cells and Kupffer cells might be ascribed to the functions of these cells and is not significantly modified by monensin. In conclusion, the altered cross-talk between sinusoidal cells in liver pathology might involve retinol as well as cytokines. Different pools of dolichol might have a role in this membrane process in a hydrophobic environment.
Department of Experimental Medicine, University of Genoa, Italy.
A
A
Casu
C
C
Canepa
F
F
Majorani
G
G
Nanni
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004286:Dolichols / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000737:chemistry / Q000187:drug effects; D013997:Time Factors; D014801:Vitamin A / Q000378:metabolism*
D004286:Dolichols; D014801:Vitamin A; D008985:Monensin