Nascent VLDL phospholipid composition is altered when phosphatidylcholine biosynthesis is inhibited: evidence for a novel mechanism that regulates VLDL secretion.
Previous work has shown that inhibition of phosphatidylcholine biosynthesis inhibits very low density lipoprotein (VLDL) secretion by causing a decrease in the number of particles in the Golgi but not in the endoplasmic reticulum of rat liver (Verkade et al. (1993) J. Biol. Chem. 268, 24,990-24,996). One explanation for this observation was that VLDL from choline deficient livers was degraded in a post-endoplasmic reticulum compartment. This hypothesis was supported by experiments in which choline deficient (CD) or choline supplemented (CS) rat hepatocytes were incubated +/- Brefeldin A. In the presence of Brefeldin A, VLDL secretion was blocked, but no difference was observed in the degradation of apolipoprotein B (apoB) within the CD or CS cells. If increased catabolism of apoB were occurring in the endoplasmic reticulum of CD hepatocytes, enhanced degradation of apoB in CD cells might have been expected. Inhibition of phosphatidylcholine biosynthesis also caused decreases in the phosphatidylcholine content of membranes of the secretory pathway. The lipids of nascent VLDLs from the lumina of endoplasmic reticulum and Golgi prepared from CD rat liver were relatively enriched in phosphatidylethanolamine and depleted of phosphatidylcholine when compared to samples from CS liver. The changes in nascent VLDL phospholipid composition mimicked that of the organelle membranes from which the VLDLs were isolated. Possibly the phospholipid composition of the organelles is a factor in determining the final phospholipid composition of VLDLs. One hypothesis is that when phosphatidylcholine biosynthesis is impaired, nascent VLDL is assembled incorrectly and degraded by a quality control protease in a post-endoplasmic reticulum compartment.
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Lipid and Lipoprotein Research Group, University of Alberta, Edmonton, Canada.
Vance
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D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D002451:Cell Compartmentation; D002794:Choline / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001055:Apolipoproteins B; D008079:Lipoproteins, VLDL; D010713:Phosphatidylcholines; D002794:Choline