Apolipoprotein(a) synthesis and secretion from hepatoma cells is coupled to triglyceride synthesis and secretion.
Apolipoprotein(a) (apo(a)) is synthesized and secreted from liver cells and represents one of the two major protein components of the atherogenic lipoprotein, Lp(a). Little is known, however, of the factors that regulate the secretion of this protein. We have undertaken an analysis of the response to oleate supplementation in stable clones of HepG2 and McA-RH7777 cells expressing either a 6 K-IV or 17 K-IV isoform of apo(a). These cell lines were examined by pulse-chase analysis and each demonstrated an increase (range 2-6-fold) in apo(a) secretion following supplementation with 0.8 mM oleate. Microsomal membranes, prepared from HepG2 cells expressing a 6 K-IV apo(a) isoform, demonstrated that oleate supplementation increased the apparent protection of apo(a) from protease digestion, suggesting that alterations in the translocation efficiency of apo(a) may accompany the addition of oleate. Cells incubated with brefeldin A demonstrated increased recovery of the precursor form of apo(a) with oleate supplementation, suggesting that alterations in post-translational degradation may also contribute to the observed increase in apo(a) secretion following oleate addition. To further characterize the oleate-dependent increase in apo(a) secretion, cells were incubated with an inhibitor of the microsomal triglyceride transfer protein. These experiments demonstrated a dose-dependent decrease in apo(a) secretion from both cell lines. Furthermore, addition of either the microsomal triglyceride transfer protein inhibitor or triacsin C, an inhibitor of acyl-CoA synthase, completely abrogated the oleate-dependent increase in apo(a) secretion. Taken together, these data provide evidence that apo(a) secretion from hepatoma cells may be linked to elements of cellular triglyceride assembly and secretion.
Nassir
F
F
Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Bonen
D K
DK
Davidson
N O
NO
D001053:Apolipoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D053241:Apoprotein(a); D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D017270:Lipoprotein(a); D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid / Q000008:administration & dosage / Q000494:pharmacology; D014162:Transfection; D014280:Triglycerides / Q000096:biosynthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001053:Apolipoproteins; D017270:Lipoprotein(a); D014280:Triglycerides; D019301:Oleic Acid; D053241:Apoprotein(a)