Inhibition of secretion of truncated apolipoproteins B by monomethylethanolamine is independent of the length of the apolipoprotein.
Translocation of apolipoprotein (apo) B across the endoplasmic reticulum membrane is a likely site for regulation of secretion of very low density lipoproteins from the liver. When primary rat hepatocytes are enriched with the phospholipid phosphatidylmonomethylethanolamine, the secretion of apoB, but not other proteins such as apoprotein A1 and albumin, is disrupted (Vance, J. E. (1991) J. Lipid Res. 32, 1971-1982). Moreover, less apoB enters the microsomal lumen and the intracellular degradation of apoB is increased (Rusiñol, A. E., Chan, E. Y. W., and Vance, J. E. (1993a) J. Biol. Chem. 268, 25168-25175). In the present study we have used McArdle 7777 rat hepatoma cells stably transfected with carboxyl-terminal-truncated variants of human apoB100 and have demonstrated that the reduction in apoB secretion induced by phosphatidylmonomethylethanolamine is not a function of assembly of the apoB into a buoyant lipoprotein particle. In addition, inhibition of the intracellular degradation of the apoproteins B does not restore apoB secretion, suggesting that the effect of phosphatidylmonomethylethanolamine enrichment on apoB degradation is secondary to the effect on translocation of the protein into the endoplasmic reticulum lumen. Furthermore, supplementation of the culture medium with oleic acid does not increase apoB secretion, reduce the intracellular degradation of apoB or reverse the effects of phosphatidylmonomethylethanolamine enrichment on these processes. Our data support the hypothesis that translocation of apoB protein across the endoplasmic reticulum membrane, regardless of the association of the apoB with neutral lipids, may be a key regulatory step in very low density lipoprotein secretion.
Rusiñol
A E
AE
Lipid and Lipoprotein Research Group, University of Alberta, Edmonton, Canada.
Vance
J E
JE
D000818:Animals; D001055:Apolipoproteins B / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D007425:Intracellular Membranes / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D051381:Rats; D014357:Trypsin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D001055:Apolipoproteins B; D004983:Ethanolamines; D009829:Oleic Acids; D019301:Oleic Acid; D014357:Trypsin; C017500:N-methylaminoethanol