© 1995 American Heart Association, Inc.
Articles |
Level of Apolipoprotein B mRNA Has an Important Effect on the Synthesis and Secretion of Apolipoprotein B–Containing Lipoproteins
Studies on Transfected Hepatoma Cell Lines Expressing Recombinant Human Apolipoprotein B
From the Lipid and Lipoprotein Research Group and Department of Biochemistry, University of Alberta, Edmonton, Canada.
Correspondence to Dr Zemin Yao, Lipoprotein and Atherosclerosis Group, University of Ottawa Heart Institute, 1053 Carling Ave, Ottawa, Ontario, Canada K1Y 4E9. E-mail zyao@heartinst.on.ca.
Abstract The effect of apoB mRNA level on hepatic apoB production has not been studied extensively, primarily because the steady state level of apoB mRNA cannot be altered on a short-term basis. We studied the effect of vastly different apoB mRNA levels on the synthesis and secretion of apoB-containing lipoproteins using rat hepatoma (McA-RH7777) cell lines transfected with cDNA constructs encoding human apoB53 (the amino-terminal 53% of the protein; hapoB53) or apoB100 (hapoB100). Among the three hapoB53-transfected cell lines, the relative steady state levels of the hapoB53 mRNA were 10:2.5:<0.1. Correspondingly, the relative concentration of the intracellular hapoB53 protein was 8:3:1 and of the medium hapoB53 (accumulated over a period of 18 hours) was 12:4:1, which positively correlates with the hapoB53 mRNA levels. The expression level of hapoB53 did not affect the buoyant density of lipoproteins containing hapoB53 (d=1.06 to 1.21 g/mL) or endogenous rat apoB100 (d<1.06 g/mL). When cell lines containing high or intermediate hapoB53 mRNA levels were compared, there was an eightfold increase in the synthesis and a twofold increase in the secretion efficiency of hapoB53. Analysis of the synthesis and secretion of lipids revealed that in cells producing high levels of hapoB53, triglyceride synthesis (twofold) and secretion (twofold to threefold) were also increased. Furthermore, with the three hapoB100-transfected cells we also observed an increase in apoB100 synthesis (threefold), apoB100 secretion efficiency (twofold), triglyceride synthesis (fourfold to fivefold), and triglyceride secretion (fourfold to fivefold) in the cells expressing high levels of hapoB100. In all the cell lines examined, secretion efficiency of endogenous rat apoA-I was not affected by transfection. Together these data suggest that secretion of apoB-containing triglyceride-rich lipoproteins can be influenced by the level of apoB mRNA or the rate of apoB translation.
Key Words: human apoB53 • human apoB100 • recombinant DNA • rat hepatoma • transfection • lipogenesis
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