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J Biol Chem, Vol. 273, Issue 28, 17793-17800, July 10, 1998
From the Department of Medicine, University of Chicago,
Chicago, Illinois 60637
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.
Apolipoprotein(a) Synthesis and Secretion from Hepatoma Cells Is
Coupled to Triglyceride Synthesis and Secretion
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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