Huh-7 or HepG2 cells: which is the better model for studying human apolipoprotein-B100 assembly and secretion?

Abstract

This article is available online at http://www.jlr.org teins (VLDL) from liver. From a clinical perspective, plasma apoB100 levels and the apoB100/apoA1 ratio are superior to any other lipoprotein-related indices used to estimate risk of acute myocardial infarction ( 1 ). This illustrates the need for a deep understanding of the cellular mechanisms that regulate apoB100 production and secretion. Although rat hepatoma McA-RH7777 cells secrete much of their apoB100 as buoyant VLDL, it would be desirable to have a similar cell line of human origin. Many studies of human apoB100 metabolism have used the hepatoma HepG2 cell line. Despite their general use, however, HepG2 cells secrete relatively dense, lipid-poor apoB100-containing particles, unlike the buoyant VLDL particles secreted in vivo by mammalian liver. An alternative human cell model with a more native level of VLDL secretion would strongly benefi t the lipoprotein fi eld and might advance novel insights into apoB100 metabolism.Recently, Huh-7 cells were proposed as a superior human hepatic cell model for the study of apoB100 metabolism and VLDL secretion [see references 2, 3)] and are becoming more widely used for these purposes [see references ( 4, 5 )]. To our knowledge, however, there have been no published studies of the basic characteristics of Huh-7 cells with regard to apoB100 and VLDL metabolism. In the present report, we have fi lled this gap in knowledge and also have compared the results to those with HepG2 cells. Based on the available evidence, Huh-7 cells resemble HepG2 cells in many respects, with neither cell Apolipoprotein-B100 (apoB100) is the essential protein for the assembly and secretion of very low density lipopro- Abbreviations: apoB100, apolipoprotein-B100; MEK-ERK, mitogenactivated protein kinase kinase-extracellular signal regulated kinase; MTP, microsomal triglyceride transfer protein; OA, oleic acid.

Characterization of Hepatitis C Virus Particle Subpopulations Reveals Multiple Usage of the Scavenger Receptor BI for Entry Steps

“…Although there may be differences between HCVcc and patient-derived particles, e.g. in their apolipoprotein composition of viral subpopulations of different densities, as HCVcc-producing hepatocarcinoma cells are impaired at late steps of VLDL biogenesis and production (7,87,88), our study further extends these previous results (28) and underscores the notion that distinct capture molecules are used by the different HCV subpopulations to induce attachment to target cells. Although attachment of HCVcc of intermediate density, particularly, seems to be mediated by SR-BI, we found that the infectivity of low density HCVcc particles also involves a VLDL-derived component as it could be competed by VLDL and/or by purified apoE.…”

Entry and replication of recombinant hepatitis C viruses in cell culture

“…New models such as the partially polarized and HCV-permissive HepG2 CD81/miR-122 cell line might help tackling this concern [112]. Furthermore, despite some controversy, it is generally accepted that the VLDL secretion is altered in the Huh-7 cell line [28,166]. A similar defect is observed in the HepG2 cell line, also it can be partially rescued by inhibition of MEK-ERK (mitogen-activated protein kinase kinase -extracellular signal regulated kinase) [166].…”

“…Furthermore, despite some controversy, it is generally accepted that the VLDL secretion is altered in the Huh-7 cell line [28,166]. A similar defect is observed in the HepG2 cell line, also it can be partially rescued by inhibition of MEK-ERK (mitogen-activated protein kinase kinase -extracellular signal regulated kinase) [166]. As a consequence, HCV particles produced in Huh-7-derived cell lines do not fully resemble the lipoviroparticles circulating in infected patient serum, with possible implications for entry studies.…”

Functional and Biochemical Characterization of Hepatitis C Virus (HCV) Particles Produced in a Humanized Liver Mouse Model

“…However, most of these cell lines have impaired production of VLDL because they express pre-VLDLs that are not fully lipidated and that do not fuse with apoE-containing luminal lipid droplets (30). The resulting HCVcc particles are thus poorly associated with apoB (9), and their buoyant density profile is significantly different compared with in vivo recovered viruses (31,32).…”