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

Apolipoprotein-B100 (apoB100) is the essential protein for the assembly and secretion of very low density lipoproteins (VLDL) from liver. The hepatoma HepG2 cell line has been the cell line of choice for the study of synthesis and secretion of human apoB-100. Despite the general use of HepG2 cells to study apoB100 metabolism, they secrete relatively dense, lipid-poor particles compared with VLDL secreted in vivo. Recently, Huh-7 cells were adopted as an alternative model to HepG2 cells, with the implicit assumption that Huh-7 cells were superior in some respects of lipoprotein metabolism, including VLDL secretion. In this study we addressed the hypothesis that the spectrum of apoB100 lipoprotein particles secreted by Huh-7 cells more closely resembles the native state in human liver. We find that Huh-7 cells resemble HepG2 cells in the effects of exogenous lipids, microsomal triglyceride transfer protein (MTP)-inhibition, and proteasome inhibitors of apoB100 secretion, recovery, and degradation. In contrast to HepG2 cells, however, MEK-ERK inhibition does not correct the defect in VLDL secretion. Huh-7 cells do not appear to offer any advantages over HepG2 cells as a general model of human apoB100-lipoprotein metabolism. Apolipoprotein-B100 (apoB100) is the essential protein for the assembly and secretion of very low density lipoproteins (VLDL) from liver. The hepatoma HepG2 cell line has been the cell line of choice for the study of synthesis and secretion of human apoB-100. Despite the general use of HepG2 cells to study apoB100 metabolism, they secrete relatively dense, lipid-poor particles compared with VLDL secreted in vivo. Recently, Huh-7 cells were adopted as an alternative model to HepG2 cells, with the implicit assumption that Huh-7 cells were superior in some respects of lipoprotein metabolism, including VLDL secretion. In this study we addressed the hypothesis that the spectrum of apoB100 lipoprotein particles secreted by Huh-7 cells more closely resembles the native state in human liver. We find that Huh-7 cells resemble HepG2 cells in the effects of exogenous lipids, microsomal triglyceride transfer protein (MTP)-inhibition, and proteasome inhibitors of apoB100 secretion, recovery, and degradation. In contrast to HepG2 cells, however, MEK-ERK inhibition does not correct the defect in VLDL secretion. Huh-7 cells do not appear to offer any advantages over HepG2 cells as a general model of human apoB100-lipoprotein metabolism. Apolipoprotein-B100 (apoB100) is the essential protein for the assembly and secretion of very low density lipoproteins (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 (1McQueen M.J. Hawken S. Wang X. Ounpuu S. Sniderman A. Probstfield J. Steyn K. Sanderson J.E. Hasani M. Volkova E. for the INTERHEART study investigators Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study.Lancet. 2008; 372: 224-233Abstract Full Text Full Text PDF PubMed Scopus (639) Google Scholar). 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 benefit the lipoprotein field 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 2Ohsaki Y. Cheng J. Fujita A. Tokumoto T. Fujimoto T. Cytoplasmic lipid droplets are sites of convergence of proteasomal and autophagic degradation of apolipoprotein B.Mol. Biol. Cell. 2006; 17: 2674-2683Crossref PubMed Scopus (166) Google Scholar, 3Higashi Y. Itabe H. Fukase H. Mori M. Fujimoto Y. Sato R. Imanaka T. Takano T. Distribution of microsomal triglyceride transfer protein within sub-endoplasmic reticulum regions in human hepatoma cells.Biochim. Biophys. Acta. 2002; 1581: 127-136Crossref PubMed Scopus (14) Google Scholar)] and are becoming more widely used for these purposes [see references (4Ohsaki Y. Cheng J. Suzuki M. Fujita A. Fujimoto T. Lipid droplets are arrested in the ER membrane by tight binding of lipidated apolipoprotein B-100.J. Cell Sci. 2008; 121: 2415-2422Crossref PubMed Scopus (127) Google Scholar, 5Lalanne F. Lambert G. Amar M.J. Chétiveaux M. Zaïr Y. Jarnoux A.L. Ouguerram K. Friburg J. Seidah N.G. Brewer Jr, H.B. Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cells.J. Lipid Res. 2005; 46: 1312-1319Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar)]. 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 filled 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 line having obvious superiority as the model of normal human liver apoB100 and VLDL metabolism. Dimethyl sulfoxide (DMSO) and the proteasomal inhibitor MG132 (Z-Leu-Leu-Leu-al) were obtained from Sigma (St. Louis, MO). Complete Protease Inhibitor Cocktail Tablets were obtained from Roche (catalog no. 1836153; Indianapolis, IN). Protein A Sepharose was obtained from GE Healthcare (Uppsala, Sweden). The [35S]methionine/cysteine protein labeling mixture was obtained from Perkin-Elmer Life Sciences (Waltham, MA). Goat anti-human apoB100 polyclonal antibody was from Calbiochem (catalog no. 178467). Goat anti-human albumin antibody was obtained from Midland Bioproducts Corp. (catalog no. 71907). The microsomal triglyceride transfer protein (MTP) inhibitor was provided by BristolMyers-Squibb (designated compound no. 9 in the study by Wetterau et al.) (6Wetterau J.R. Gregg R.E. Harrity T.W. Arbeeny C. Cap M. Connolly F. Chu C.H. George R.J. Gordon D.A. Jamil H. An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits.Science. 1998; 282: 751-754Crossref PubMed Scopus (251) Google Scholar). The mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK-ERK) inhibitor PD98059 was purchased from Calbiochem (San Diego, CA). HepG2 cells were obtained from American Type Culture Collection (Manassas, VA). Huh-7 cells were a kind gift from Dr. Z. Yao (University of Ottawa, ON, Canada). HepG2 and Huh-7 cells were maintained in Dulbecco's modification of Eagle's medium (DMEM; Cellgro, Manassas, VA) containing 1% l-glutamine, 10% fetal bovine serum, 100 units/ml penicillin, 100 μg/ml streptomycin in 5% Co2 at 37°C. The medium was changed every 3 days. HepG2 and Huh-7 cells were grown on 100-mm tissue culture dishes and preincubated for 1 h in low-serum medium (1% fetal bovine serum, 1% l-glutamine). Cells were labeled with 150–200 μCi of sulfur-35 protein labeling mixture/ml of medium for 3 h. To promote lipid loading of apoB100-containing lipoproteins, cells were incubated with oleic acid (OA) complexed to BSA (0.6 mM OA; OA/BSA molar ratio 5:1) or incubated with BSA as a control during the metabolic labeling period. To examine the effect of MEK-ERK inhibition on VLDL assembly, cells were preincubated overnight with 5 μM PD98059 inhibitor in DMSO. The same concentration of PD98059 was present in the medium during the 3-h labeling period. Equal volumes from each dish of conditioned medium were harvested, and 0.5 ml of human plasma (from outdated plasma obtained from the Tisch Hospital Blood Bank) was added as a carrier. A total of 4 ml of the sample was then adjusted to a density (d) of 1.2 g/l with KBr and loaded onto the bottom of a Beckman model SW41 centrifuge tube. The sample was overlaid with 2.5 ml KBr at d = 1.065, 2.5 ml of KBr at d = 1.02, and 2.5 ml of KBr at d = 1.006. All solutions contained 2 mM EDTA. After ultracentrifugation (20 h, 15°C, 173,000 g), lipoproteins were collected from top to bottom in 11 fractions. 35S-apoB100 in each fraction was immunoprecipitated, as described below. Pulse-chase studies of HepG2 and Huh-7 cells were performed to investigate the effects of various metabolic perturbations on the synthesis and degradation of apoB100. The time required to reach maximal incorporation of radioactive isotope in apoB100 protein varies from 15 min in rat hepatoma McA-RH7777cells to 20 min in primary rat hepatocytes and 30 min in primary mouse hepatocytes (7Pan M. Cederbaum A.I. Zhang Y.L. Ginsberg H.N. Williams K.J. Fisher E.A. Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production.J. Clin. Invest. 2004; 113: 1277-1287Crossref PubMed Scopus (232) Google Scholar). In order to accurately determine the peak incorporation of radioactive isotope in apoB100 in HepG2 and Huh-7 cell lines, we varied our initial chase point from 5 to 30 min, with sampling at 5-min intervals (supplemental Fig. SI). The peak amount of radiolabeled apoB100 in both types of cells was recovered at 10–15 min. Accordingly, we chose 13 min as our standard initial chase point for all pulse-chase experiments with HepG2 and Huh-7 cells. For subsequent experiments in this study, cells were preincubated for 1 h (37°C, 5% Co2) in low-serum DMEM (1% fetal bovine serum, 1% l-glutamine), washed twice with ice-cold PBS, and then labeled for 15 min with methionine/cysteine-free DMEM (1% fetal bovine serum, 1% l-glutamine) supplemented with ∼300 μCi of 35S protein labeling mixture/ml of medium at 37°C, under 5% Co2. After the labeling period, the medium was removed, and cells were washed twice with ice-cold PBS. Cells were subsequently incubated with chase medium (Met/Cys-free DMEM, 1% fetal bovine serum, 1% l-glutamine) supplemented with an excess amount of unlabeled methionine (1.5 mg/ml) and cysteine (0.5 mg/ml). The durations of the chase periods are shown in the appropriate figure legends. When the OA stimulation of lipid synthesis and lipoprotein lipid loading were assessed, 0.6 mM OA complexed to BSA (molar ratio, 5:1) was provided throughout the course of the experiment. In some experiments, 25 μM MG132 (Sigma) and 10 nM of an MTP inhibitor (provided by Bristol­Myers-Squibb; designated compound no. 9 in the study by Wetterau et al. (6Wetterau J.R. Gregg R.E. Harrity T.W. Arbeeny C. Cap M. Connolly F. Chu C.H. George R.J. Gordon D.A. Jamil H. An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits.Science. 1998; 282: 751-754Crossref PubMed Scopus (251) Google Scholar)) were present throughout the course of the experiment as indicated in Results and shown in appropriate figures. At the end of the chase period, medium samples were collected, supplemented with fresh PMSF (1 mM), and centrifuged at 10,000 rpm for 5 min in a table-top centrifuge to remove debris. Cells were washed twice with ice-cold PBS and lysed in cell lysis buffer (10 mM PBS, pH 7.4, 125 mM NaCl, 36 mM lithium dodecyl sulfate, 24 mM deoxycholate, and 1% Triton X-100) freshly supplemented with protease inhibitor cocktail available from and 1 mM cells, in their were on for 30 min, then a to an and centrifuged at 10,000 rpm for 5 min in a table-top To cell or conditioned medium was with buffer mM NaCl, 5 mM mM 1% Triton and 5 of serum, and protein A A buffer was with cell or conditioned medium to reach a concentration of buffer in the The mixture was incubated overnight with at The the were washed with and were with sample buffer pH 1 mM 10 mM 25 mM by the samples to for 5 min. of labeled apoB100 was performed by and protein synthesis was by of acid in of cell and conditioned results are as For were were performed to the of apoB100 secreted by HepG2 and Huh-7 cells. Cells were in At the time of the experiment cells were washed twice with PBS and incubated for 3 h in 15 ml of DMEM and 1% fetal bovine At the end of the apoB100 in the conditioned medium was an from The of apoB100 was to the protein in the cell by We the hypothesis that the buoyant density of apoB100-containing lipoprotein particles secreted by Huh-7 cells more closely resembles that of VLDL particles secreted by human liver in in contrast to the particles secreted by HepG2 cells. For this HepG2 and Huh-7 cells were labeled with [35S]methionine/cysteine for 3 h in the or of complexed to Equal volumes of conditioned medium were then to density and apoB100 was recovered from each fraction HepG2 cells secreted of their apoB100 as lipoproteins with density of compared with secreted by Huh-7 cells. The amount of apoB100 secreted as particles was in both HepG2 and Huh-7 cells under lipid loading with OA h, 0.6 mM), both HepG2 and Huh-7 cells their apoB100 secretion by more in the and density lipoprotein from to lipid loading in HepG2 cells but from to in Huh-7 cells. lipid loading a density of secreted particles in HepG2 cells in Despite the apoB100 in the density from the conditioned medium of HepG2 cells, to cell Huh-7 cells secrete more apoB100 cell HepG2 cells cell that the the of radiolabeled apoB100 in volumes of medium and are not for in cell protein or as the An the cell types was the density in conditioned medium samples of with lipoproteins of all The secretion were in HepG2 and with the levels in the of apoB100 is at the level of degradation E.A. Ginsberg H.N. in the the assembly and secretion of apolipoprotein Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, Fisher E.A. The many apolipoprotein B secretion and 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). In HepG2 cells the proteasome has been in the degradation of apoB100 Fisher E.A. The many apolipoprotein B secretion and 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). of lipid the apoB100 is and to the proteasome for degradation M. Fisher E.A. Ginsberg H.N. of apolipoprotein A for proteasomal degradation of a Biol. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). In of an inhibitor of the proteasomal degradation apoB100 from many cells, exogenous of OA strongly apoB100 secretion in E.A. Ginsberg H.N. in the the assembly and secretion of apolipoprotein Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). We to the effects of OA and a proteasomal inhibitor on apoB100 secretion and degradation in HepG2 and Huh-7 cells. The pulse-chase experiments in Fig. 3 that under of lipid apoB100 is in both HepG2 and Huh-7 cells 1 and the amount of apoB100 in the cell at 13 min chase with the amount of apoB100 in cell medium at min the of apoB100 that is secreted 3 h of chase compared with the peak amount of apoB100 recovered from the cell is 10% in both HepG2 and Huh-7 cells under standard culture 1 and the amount of apoB100 at 13 min of chase with the amount of apoB100 in the medium at min of The of proteasomal degradation is strongly by the of for apoB100 E.A. M. X. S. Wang H. A.L. Ginsberg H.N. The degradation of apolipoprotein is by the and protein Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). with E. M. Fisher E.A. acid lipoprotein secretion by degradation and triglyceride Lipid Res. 2002; Full Text Full Text PDF PubMed Scopus Google we that OA the synthesis = and secretion of apoB100 and twice as much apoB100 from degradation 3 3 and 4 to 1 and A similar effect was in Huh-7 cells 3 and 4 to The proteasome inhibitor MG132 apoB100 synthesis as as the from and cell in HepG2 and Huh-7 cells = with the of proteasomal degradation in both cell to For the in these are with proteasomal degradation in Fisher E.A. The many apolipoprotein B secretion and 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). to promote apoB100 of the level of lipid is to the transfer of to the apoB100 by inhibition of MTP F. T. degradation of apolipoprotein by the proteasome is by microsomal triglyceride transfer studies on HepG2 cells with an inhibitor of microsomal triglyceride transfer Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, C. X. M. Wang H. Fisher E.A. The inhibition of microsomal triglyceride transfer protein in rat hepatoma cells proteasomal and degradation of 2002; PubMed Scopus Google Scholar, M. R. Wang H. Ginsberg H.N. Fisher E.A. has a with the during and from on the microsomal triglyceride transfer protein to Sci. 1998; PubMed Scopus Google Accordingly, both HepG2 and Huh-7 cells, we the effects of a MTP inhibitor on apoB100 secretion and apoB100 degradation and the by apoB100 degradation be cells were with an inhibitor of the To this we concentration of MTP inhibitor apoB100 secretion in HepG2 and Huh-7 cells. In both cell 10 nM compound no. 9 secretion of apoB100 in the medium 3 h of chase (supplemental Fig. inhibition of MTP to apoB100 synthesis in in Huh-7 = proteasomal degradation M. Fisher E.A. Ginsberg H.N. of apolipoprotein A for proteasomal degradation of a Biol. 1998; Full Text Full Text PDF PubMed Scopus Google apoB100 secretion, and apoB100 degradation to in HepG2 and in Huh-7 both in the and of OA of proteasomal inhibitor MG132 strongly the synthesis of apoB100 in and in and the amount of apoB100 that be recovered from and cells 3 h of chase the of the proteasome in the degradation of both and M. Fisher E.A. Ginsberg H.N. of apolipoprotein A for proteasomal degradation of a Biol. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. Fisher E.A. G. M. H. degradation the reticulum from protein 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). To that the effects of proteasomal or MTP inhibition were we also albumin as a control protein from the same of the secretion, or of albumin from HepG2 or Huh-7 cells of the MEK-ERK was as a to VLDL secretion in HepG2 cells J. R. K. MEK-ERK inhibition the defect in VLDL assembly in HepG2 of in Biol. PubMed Scopus Google Scholar). We this effect of MEK-ERK inhibition is to HepG2 or is to Huh-7 cells as shown in Fig. PD98059 a in VLDL secretion in HepG2 cells this was not in Huh-7 cells. is that the standard cell model for the study of human apoB100-lipoprotein metabolism, LDL and density apoB100-containing particles, unlike normal human apoB100 with VLDL In this study, we addressed the hypothesis that the density of apoB100 lipoprotein particles secreted by Huh-7 cells more closely resembles that of The study was by the use of this cell line as an alternative model to HepG2 cells Y. Cheng J. Fujita A. Tokumoto T. Fujimoto T. Cytoplasmic lipid droplets are sites of convergence of proteasomal and autophagic degradation of apolipoprotein B.Mol. Biol. Cell. 2006; 17: 2674-2683Crossref PubMed Scopus (166) Google Scholar, 3Higashi Y. Itabe H. Fukase H. Mori M. Fujimoto Y. Sato R. Imanaka T. Takano T. Distribution of microsomal triglyceride transfer protein within sub-endoplasmic reticulum regions in human hepatoma cells.Biochim. Biophys. Acta. 2002; 1581: 127-136Crossref PubMed Scopus (14) Google Scholar, Y. Cheng J. Suzuki M. Fujita A. Fujimoto T. Lipid droplets are arrested in the ER membrane by tight binding of lipidated apolipoprotein B-100.J. Cell Sci. 2008; 121: 2415-2422Crossref PubMed Scopus (127) Google Scholar, 5Lalanne F. Lambert G. Amar M.J. Chétiveaux M. Zaïr Y. Jarnoux A.L. Ouguerram K. Friburg J. Seidah N.G. Brewer Jr, H.B. Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cells.J. Lipid Res. 2005; 46: 1312-1319Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar, Y. Itabe H. Fukase H. Mori M. Fujimoto Y. Takano T. lipid transfer is for during very low density lipoprotein assembly in Biol. Full Text Full Text PDF PubMed Scopus Google with the implicit assumption that Huh-7 are more native in their apoB100 levels are by degradation E.A. Ginsberg H.N. in the the assembly and secretion of apolipoprotein Biol. 2002; Full Text Full Text PDF PubMed Scopus Google characteristics of apoB100 degradation have been in HepG2 cells. studies M. R. Wang H. Ginsberg H.N. Fisher E.A. has a with the during and from on the microsomal triglyceride transfer protein to Sci. 1998; PubMed Scopus Google Scholar, M. Fisher E.A. Ginsberg H.N. The of to apolipoprotein in the assembly and secretion of lipoproteins, is of both microsomal triglyceride transfer protein and triglyceride Biol. 2002; Full Text Full Text PDF PubMed Scopus Google and our present that HepG2 cells strongly on exogenous to lipid synthesis and for lipoprotein lipid the of apoB100 is and for and degradation by the proteasome M. Fisher E.A. Ginsberg H.N. of apolipoprotein A for proteasomal degradation of a Biol. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). OA of the apoB100 from proteasomal degradation and it to be A of HepG2 cells as a model of human apoB100 metabolism is their to apoB100 and secrete with this is our that density in the of exogenous lipids, of the secreted apoB100 the density of and of secreted apoB100 was lipidated to Lipid loading the apoB100 in the VLDL fraction to A similar from 1% to was in the Huh-7 cells also secreted all apoB100 as LDL density particles under strongly apoB100 secretion, but unlike in HepG2 cells, it not a density of secreted particles in Huh-7 of the apoB100 was lipidated and secreted as VLDL and 5% as the of of apoB100 is in Huh-7 cells in HepG2 cells We that Huh-7 cells secreted apoB100 HepG2 cells This was on Fig. the of radiolabeled apoB100 from volumes of conditioned medium samples from of both cell there were of apoB100 in the HepG2 In the to cell apoB100 secretion from HepG2 cells. Based on HepG2 protein synthesis was that in Huh-7 cells, with apoB100 however, cells were in Huh-7 culture that by volumes of conditioned samples for the the cell types in the production of radiolabeled apoB100 was HepG2 cells have a production of apoB100 on a cell the of HepG2 cells in the secretion of a relatively amount of radiolabeled apoB100 culture Lipid or the of transfer of to the apoB100 in all hepatic cells to H.N. Fisher E.A. The of degradation in the of apolipoprotein B Lipid Res. Full Text Full Text PDF PubMed Scopus Google degradation of the of be by with an inhibitor of the The was as a cellular degradation for apoB100 during and M. Fisher E.A. Ginsberg H.N. of apolipoprotein A for proteasomal degradation of a Biol. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar, E. M. Fisher E.A. acid lipoprotein secretion by degradation and triglyceride Lipid Res. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, F. T. degradation of apolipoprotein by the proteasome is by microsomal triglyceride transfer studies on HepG2 cells with an inhibitor of microsomal triglyceride transfer Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, S. C. Fisher E.A. G. M. H. degradation the reticulum from protein 2006; Full Text Full Text PDF PubMed Scopus Google Scholar, degradation of apolipoprotein PubMed Scopus Google Scholar). were in the present study for HepG2 cells and to Huh-7 cells. In there were in apoB100 synthesis MG132 was present during the period, we have shown to be from degradation M. Fisher E.A. Ginsberg H.N. of apolipoprotein A for proteasomal degradation of a Biol. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar, F. T. degradation of apolipoprotein by the proteasome is by microsomal triglyceride transfer studies on HepG2 cells with an inhibitor of microsomal triglyceride transfer Biol. Full Text Full Text PDF PubMed Scopus Google as as an in apoB100 at the end of the chase Recently, MEK-ERK was to to VLDL secretion in HepG2 cells. with that J. R. K. MEK-ERK inhibition the defect in VLDL assembly in HepG2 of in Biol. PubMed Scopus Google we that inhibition of the of secreted to particles, with the effect on effect was on the lipoprotein secretion in cells, a in to VLDL or secretion the cell In we find that Huh-7 cells do not appear to offer any advantages over HepG2 cells as a general model of human apoB100-lipoprotein metabolism. In VLDL secretion in in HepG2 cells. with mitogen-activated protein kinase kinase microsomal triglyceride transfer protein oleic acid

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