The effects of monensin on secretion of very-low-density lipoprotein and metabolism of asialofetuin by cultured rat hepatocytes.
Primary cultures of rat hepatocytes were used to study secretion of very-low-density lipoproteins and metabolism of asialofetuin. The ionophore monensin inhibited both secretion of very-low-density lipoproteins and binding and degradation of asialofetuin in a concentration-dependent manner. Secretion as well as receptor binding were markedly decreased after 15 min treatment with monensin. The inhibitory effect of the ionophore was fully reversible, and no effect on protein synthesis was observed at concentrations up to 50 microM. The secretion of apoproteins (B-small, B-large and E) and that of albumin were inhibited to the same extent as was triacylglycerol secretion. Secretion of very-low-density lipoproteins was more sensitive to low concentrations of monensin than was the metabolism of asialofetuin. Maximum inhibition of very-low-density-lipoprotein secretion was obtained at 5-10 microM-monensin, whereas 25 microM was required to obtain maximum inhibition of binding and degradation of asialofetuin. The number of surface receptors for asialofetuin decreased to about half when the cells were exposed to 25 microM-monensin. It is possible that monensin inhibits endo- and exo-cytosis via a similar mechanism, e.g. by disturbing proton gradients. Since secretion of very-low-density lipoproteins was more sensitive to low concentrations of monensin, it is likely that monensin independently inhibits endocytic and secretory functions in cultured hepatocytes.
A C
AC
Rustan
J O
JO
Nossen
T
T
Berg
C A
CA
Drevon
D000818:Animals; D001212:Asialoglycoproteins; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D060748:Fetuins; D005663:Furans / Q000494:pharmacology*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000096:biosynthesis; D000509:alpha-Fetoproteins / Q000378:metabolism*
D001212:Asialoglycoproteins; D060748:Fetuins; D005663:Furans; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D000509:alpha-Fetoproteins; C017029:asialofetuin; D008985:Monensin