INHIBITION OF SECRETION OF TRUNCATED APOLIPOPROTEINS-B BY MONOMETHYLETHANOLAMINE IS INDEPENDENT OF THE LENGTH OF THE APOLIPOPROTEIN

Translocation of apolipoprotein (ape) B across the endoplasmic reticul um membrane is a likely site for regulation of secretion of very low d ensity lipoproteins from the liver. When primary rat hepatocytes are e nriched with the phospholipid phosphatidylmonomethylethanolamine, the secretion of apoB, but not other proteins such as apoprotein Al and al bumin, 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 (Rusinol, 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 de monstrated that the reduction in apoB secretion induced by phosphatidy lmonomethylethanolamine is not a function of assembly of the apoB into a buoyant Lipoprotein particle. In addition, inhibition of the intrac ellular degradation of the apoproteins B does not restore apoB secreti on, suggesting that the effect of phosphatidylmonomethylethanolamine e nrichment on apoB degradation is secondary to the effect on translocat ion of the protein into the endoplasmic reticulum lumen. Furthermore, supplementation of the culture medium with oleic acid does not increas e apoB secretion, reduce the intracellular degradation of apoB or reve rse the effects of phosphatidylmonomethylethanolamine enrichment on th ese processes. Our data support the hypothesis that translocation of a poB protein across the endoplasmic reticulum membrane, regardless of t he association of the apoB with neutral lipids, may be a key regulator y step in very low density lipoprotein secretion.