Lipoprotein synthesis and secretion by cultured rat hepatocytes. Parallel inhibition of secretion of VLDL, HDL and albumin by monensin.
The biosynthesis and secretion of very-low-density lipoproteins (VLDL) and high-density lipoproteins (HDL) by cultured normal rat hepatocytes was investigated with particular emphasis on its modification by monensin. This acidic ionophore coordinately inhibited the rates of secretion of the several VLDL apolipoproteins and the VLDL lipids, suggesting an effect late in the process of biosynthesis and secretion, probably at the stage of exiting from the Golgi apparatus. The secretion of immunoreactive albumin into the medium was comparably inhibited, implying that the pathway and mechanisms involved in albumin secretion may be closely similar to those for VLDL synthesis and secretion. Secretion of phospholipids and of apolipoproteins E and A-I in the HDL fraction increased progressively with time over 18 h in control incubations but was strongly inhibited by monensin. During extended incubation with monensin at high concentrations (10 microM), there was a net release to the medium of a number of hepatocyte proteins, including some that comigrated with apolipoprotein A-I and apolipoprotein C, making it appear that monensin increased the secretion of these apolipoproteins. However, using labeled amino acids, it was shown by autoradiography and by immunoprecipitation that secretion of newly-synthesized, radioactive apolipoprotein A-I and apolipoprotein C was actually inhibited by monensin. These results are compatible with the conclusion that HDL synthesis and secretion may occur by mechanisms closely related to those for synthesis and secretion of albumin and VLDL.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D005260:Female; D005663:Furans / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000096:biosynthesis* / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000096:biosynthesis* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008970:Molecular Weight; D008985:Monensin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000096:biosynthesis* / Q000378:metabolism
D000596:Amino Acids; D005663:Furans; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; D012709:Serum Albumin; D008985:Monensin