Biogenesis of lipoprotein(a) in human and animal hepatocytes

Electrophoresis
E M Lobentanz, H Dieplinger

Abstract

The atherogenic plasma lipoprotein complex Lp(a) consists of low density lipoprotein (LDL) and the highly polymorphic glycoprotein apolipoprotein(a) covalently linked by a disulfide bridge. A size polymorphism of apolipoprotein(a) results from a variable number of tandemly arranged kringle IV repeats. The largely varying plasma concentration of Lp(a) is nonnormally distributed in the population and correlates inversely with the molecular mass of apolipoprotein(a). In vivo turnover studies have revealed that differences in Lp(a) plasma concentrations reflect different synthesis rather than degradation. Plasma Lp(a) originates exclusively in the liver. Detailed studies of the intracellular metabolism of apolipoprotein(a) in transfected human hepatoma cells as well as in primary baboon hepatocytes have revealed an unusual secretory pathway of this protein. Due to complex folding and processing, an immature precursor form of apolipoprotein(a) is retained in the endoplasmic reticulum for a prolonged time. This retention leads to a massive accumulation in the endoplasmic reticulum which stands in contrast to most secretory proteins. Since the retention time correlates positively with the apolipoprotein(a) isoform size, this intracell...Continue Reading

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Citations

Jul 18, 2015·Atherosclerosis·Kazuhiko KotaniUNKNOWN Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group
Mar 17, 2018·Current Medicinal Chemistry·Johan G SchnitzlerJeffrey Kroon
Aug 4, 1999·Current Opinion in Lipidology·H Dieplinger, G Utermann

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