Functional analysis of the missense APOC3 mutation Ala23Thr associated with human hypotriglyceridemia

We have shown that expression of apolipoprotein (apo) C-III promotes VLDL secretion from transfected McA-RH7777 cells under lipid-rich conditions. To determine structural elements within apoC-III that confer to this function, we contrasted wild-type apoC-III with a mutant Ala23Thr originally identified in hypotriglyceridemia subjects. Although synthesis of [3H]glycerol-labeled TAG was comparable between cells expressing wild-type apoC-III (C3wt cells) or Ala23Thr mutant (C3AT cells), secretion of [3H]TAG from C3AT cells was markedly decreased. The lowered [3H]TAG secretion was associated with an inability of C3AT cells to assemble VLDL1. Moreover, [3H]TAG within the microsomal lumen in C3AT cells was 60% higher than that in C3wt cells, yet the activity of microsomal triglyceride-transfer protein in C3AT cells was not elevated. The accumulated [3H]TAG in C3AT microsomal lumen was mainly associated with lumenal IDL/LDL-like lipoproteins. Phenotypically, this [3H]TAG fractionation profiling resembled what was observed in cells treated with brefeldin A, which at low dose specifically blocked the second-step VLDL1 maturation. Furthermore, lumenal [35S]Ala23Thr protein accumulated in IDL/LDL fractions and was absent in VLDL fractions in C3AT cells. These results suggest that the presence of Ala23Thr protein in lumenal IDL/LDL particles might prevent effective fusion between lipid droplets and VLDL precursors. Thus, the current study reveals an important structural element residing within the N-terminal region of apoC-III that governs the second step VLDL1 maturation. We have shown that expression of apolipoprotein (apo) C-III promotes VLDL secretion from transfected McA-RH7777 cells under lipid-rich conditions. To determine structural elements within apoC-III that confer to this function, we contrasted wild-type apoC-III with a mutant Ala23Thr originally identified in hypotriglyceridemia subjects. Although synthesis of [3H]glycerol-labeled TAG was comparable between cells expressing wild-type apoC-III (C3wt cells) or Ala23Thr mutant (C3AT cells), secretion of [3H]TAG from C3AT cells was markedly decreased. The lowered [3H]TAG secretion was associated with an inability of C3AT cells to assemble VLDL1. Moreover, [3H]TAG within the microsomal lumen in C3AT cells was 60% higher than that in C3wt cells, yet the activity of microsomal triglyceride-transfer protein in C3AT cells was not elevated. The accumulated [3H]TAG in C3AT microsomal lumen was mainly associated with lumenal IDL/LDL-like lipoproteins. Phenotypically, this [3H]TAG fractionation profiling resembled what was observed in cells treated with brefeldin A, which at low dose specifically blocked the second-step VLDL1 maturation. Furthermore, lumenal [35S]Ala23Thr protein accumulated in IDL/LDL fractions and was absent in VLDL fractions in C3AT cells. These results suggest that the presence of Ala23Thr protein in lumenal IDL/LDL particles might prevent effective fusion between lipid droplets and VLDL precursors. Thus, the current study reveals an important structural element residing within the N-terminal region of apoC-III that governs the second step VLDL1 maturation. apolipoprotein ADP ribosylation factor 1 Ala23Thr wild-type apoC-III endoplasmic reticulum intermediate density lipoprotein calcium-independent phospholipase A2 lipoprotein lipase microsomal triglyceride-transfer protein phosphatidylcholine phospholipase D triacylglycerol Apolipoprotein (apo) C-III is a small exchangeable apolipoprotein (79 amino acids) and a major protein constituent of plasma VLDL and HDL (1Jong M.C. Hofker M.H. Havekes L.M. Role of ApoCs in lipoprotein metabolism: functional differences between ApoC1, ApoC2, and ApoC3.Arterioscler. Thromb. Vasc. Biol. 1999; 19: 472-484Crossref PubMed Scopus (431) Google Scholar). Elevated plasma apoC-III level is positively correlated with plasma triacyl­glycerol (TAG) concentration in hypertriglyceridemia subjects (2Fredenrich A. Giroux L.M. Tremblay M. Krimbou L. Davignon J. Cohn J.S. Plasma lipoprotein distribution of apoC-III in normolipidemic and hypertriglyceridemic subjects: comparison of the apoC-III to apoE ratio in different lipoprotein fractions.J. Lipid Res. 1997; 38: 1421-1432Abstract Full Text PDF PubMed Google Scholar, 3Schonfeld G. George P.K. Miller J. Reilly P. Witztum J. Apolipoprotein C–II and C–III levels in hyperlipoproteinemia.Metabolism. 1979; 28: 1001-1010Abstract Full Text PDF PubMed Scopus (144) Google Scholar). The strong correlation between plasma apoC-III and TAG levels has also been suggested in a genome-wide association studies with the Lancaster Amish population, which showed that individuals with an apoC-III null allele (R19X) had lower fasting and postprandial plasma TAG level as well as significantly reduced incidence of coronary artery calcification, which suggested that the deficiency of apoC-III could also exert an effect on cardioprotection (4Pollin T.I. Damcott C.M. Shen H. Ott S.H. Shelton J. Horenstein R.B. Post W. McLenithan J.C. Bielak L.F. Peyser P.A. et al.A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection.Science. 2008; 322: 1702-1705Crossref PubMed Scopus (523) Google Scholar). In addition, transgenic mice overexpressing human apoC-III showed severe hypertriglyceridemia and, in some cases, even hepatosteatosis (5Aalto-Setala K. Fisher E.A. Chen X. Chajek-Shaul T. Hayek T. Zechner R. Walsh A. Ramakrishnan R. Ginsberg H.N. Breslow J.L. Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles.J. Clin. Invest. 1992; 90: 1889-1900Crossref PubMed Scopus (399) Google Scholar, 6de Silva H.V. Lauer S.J. Wang J. Simonet W.S. Weisgraber K.H. Mahley R.W. Taylor J.M. Overexpression of human apolipoprotein C–III in transgenic mice results in an accumulation of apolipoprotein B48 remnants that is corrected by excess apolipoprotein E.J. Biol. Chem. 1994; 269: 2324-2335Abstract Full Text PDF PubMed Google Scholar). The positive link between plasma apoC-III and TAG levels has been attributed to apoC-III's inhibitory effect toward the activity of lipoprotein lipase (LPL) (7Ginsberg H.N. Le N.A. Goldberg I.J. Gibson J.C. Rubinstein A. Wang-Iverson P. Norum R. Brown W.V. Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo.J. Clin. Invest. 1986; 78: 1287-1295Crossref PubMed Scopus (339) Google Scholar, 8McConathy W.J. Gesquiere J.C. Bass H. Tartar A. Fruchart J.C. Wang C.S. Inhibition of lipoprotein lipase activity by synthetic peptides of apolipoprotein C–III.J. Lipid Res. 1992; 33: 995-1003Abstract Full Text PDF PubMed Google Scholar) and interference with binding/uptake of TAG-rich lipoproteins through receptor-dependent (9Sehayek E. Eisenberg S. Mechanisms of inhibition by apolipoprotein C of apolipoprotein E-dependent cellular metabolism of human triglyceride-rich lipoproteins through the low density lipoprotein receptor pathway.J. Biol. Chem. 1991; 266: 18259-18267Abstract Full Text PDF PubMed Google Scholar) and receptor-independent (10Aalto-Setala K. Weinstock P.H. Bisgaier C.L. Wu L. Smith J.D. Breslow J.L. Further characterization of the metabolic properties of triglyceride-rich lipoproteins from human and mouse apoC-III transgenic mice.J. Lipid Res. 1996; 37: 1802-1811Abstract Full Text PDF PubMed Google Scholar) endocytic pathways. Recently, cumulative in vivo and in vitro evidence suggests that the impact of apoC-III on plasma TAG concentration may from in VLDL in vivo link between apoC-III levels and VLDL was in individuals with reduced J.S. Davignon J. G. of of plasma and lipoprotein apolipoprotein C–III is to the concentration and level of of VLDL in subjects with different and levels of Clin. PubMed Scopus Google Scholar) and was also in human subjects under different R. Tremblay M. P.H. H. A. Davignon J. Cohn J.S. Plasma of apoC-III and apoE in normolipidemic and hypertriglyceridemic Lipid Res. Full Text Full Text PDF PubMed Google Scholar, P.H. Plasma apolipoprotein C–III in with very lipoprotein apolipoprotein B and lipoprotein apolipoprotein Clin. 2008; PubMed Scopus Google Scholar, J.S. Tremblay M. R. H. G. Davignon J. apoC-III is a of with Full Text Full Text PDF PubMed Scopus Google Scholar, K. of apolipoprotein triglyceride-rich lipoproteins to the of Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar, J. K. metabolic lipoproteins that apolipoproteins E and J. Clin. 2008; PubMed Scopus Google Scholar). We have in vitro evidence that apoC-III expression VLDL from cells under lipid-rich M. S. P.H. J. Wang of apolipoprotein C–III in McA-RH7777 cells VLDL and secretion under lipid-rich Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). The by which increased apoC-III expression promotes VLDL and secretion is of apoC-III has shown that the protein is of with C.S. J. M. S. G. and of human Biol. Chem. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). is amino in and in with the of lipid of human APOC3 have been H. R. L. R. M. of the properties and lipoprotein lipase inhibition of a apolipoprotein C–III Lipid Res. Full Text Full Text PDF PubMed Google Scholar, S. A. W. H. E. Mahley R.W. G. in apolipoprotein of a apoC-III in a Lipid Res. 1994; Full Text PDF PubMed Google Scholar, M. P. J. J. apolipoprotein C–III associated with hypertriglyceridemia in a of Lipid Res. 1997; 38: Full Text PDF PubMed Google Scholar, A. H. M. W. H. G. Apolipoprotein of an apolipoprotein C–III in a with Clin. Invest. 1991; PubMed Scopus Google of the Ala23Thr mutation was in subjects with hypotriglyceridemia H. R. L. R. M. of the properties and lipoprotein lipase inhibition of a apolipoprotein C–III Lipid Res. Full Text Full Text PDF PubMed Google Scholar). of the had plasma TAG that and of H. R. L. R. M. of the properties and lipoprotein lipase inhibition of a apolipoprotein C–III Lipid Res. Full Text Full Text PDF PubMed Google Scholar). The Ala23Thr mutant reduced to with inhibitory effect on in vitro activity H. R. L. R. M. of the properties and lipoprotein lipase inhibition of a apolipoprotein C–III Lipid Res. Full Text Full Text PDF PubMed Google Scholar). is on the of a region that structural with lipoprotein receptor in apoE and C.S. J. M. S. G. and of human Biol. Chem. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). studies have suggested that the Ala23Thr mutant of apoC-III to VLDL secretion under lipid-rich M. S. P.H. J. Wang of apolipoprotein C–III in McA-RH7777 cells VLDL and secretion under lipid-rich Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). The the of of mutation in VLDL has not been VLDL and the endoplasmic reticulum of TAG-rich is through a that VLDL particles through the J.L. Fisher E.A. Apolipoprotein from the endoplasmic reticulum is and to very low density lipoprotein Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, J. J.L. Fisher E.A. of very low density lipoproteins in apolipoprotein is not on apolipoprotein E.J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. G. J. L. J.C. of very low density lipoproteins apolipoprotein in McA-RH7777 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google some VLDL particles may within the J. Apolipoprotein a important apolipoprotein which lipoproteins and promotes the of PubMed Scopus Google Scholar, J. J.S. Ginsberg H.N. The of low density density lipoprotein particles to very low density lipoproteins in to in the endoplasmic reticulum and not in the in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The lipid the microsomal in the of lumenal lipid droplets H. R. and lipid characterization of apolipoprotein lipid droplets from mouse very low density lipoprotein Biol. Chem. Full Text Full Text PDF PubMed Scopus Google through a that the activity of microsomal triglyceride-transfer protein A. S. triacylglycerol protein is lumenal of not associated with as well as Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. J. J.S. of the of microsomal protein in the of mice.J. Clin. Invest. 1999; PubMed Scopus Google Scholar, K. The activity of microsomal protein is accumulation of within in McA-RH7777 cells. the of very low density Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). of and TAG has suggested that the activity is the of the of lipid droplets VLDL at the is an as second-step K. G. J. L. J.C. of very low density lipoproteins apolipoprotein in McA-RH7777 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. J.S. Fisher E.A. Ginsberg H.N. The of to apolipoprotein in the and secretion of triglyceride-rich is of microsomal protein activity and Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The second-step is to brefeldin S. K. J. inhibits the of lipoproteins in McA-RH7777 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, activity of microsomal protein is the secretion of very low density lipoproteins apolipoprotein B from McA-RH7777 Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google a that with through of with brefeldin at low dose not the of TAG-rich VLDL1 or lipoproteins K. The activity of microsomal protein is accumulation of within in McA-RH7777 cells. the of very low density Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, S. K. J. inhibits the of lipoproteins in McA-RH7777 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, activity of microsomal protein is the secretion of very low density lipoproteins apolipoprotein B from McA-RH7777 Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). In addition, the of have been shown to a in VLDL the phospholipase A2 and phospholipase D L. J. factor 1 and of phospholipase D important the of very low density Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. Wang The of very low density lipoproteins in McA-RH7777 cells is by phospholipase A2 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). of ADP ribosylation factor 1 that L. M. L. J. Role of ADP ribosylation factor 1 in the and secretion of Thromb. Vasc. Biol. PubMed Scopus Google Scholar) or with brefeldin of K. The activity of microsomal protein is accumulation of within in McA-RH7777 cells. the of very low density Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, S. K. J. inhibits the of lipoproteins in McA-RH7777 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) TAG-rich VLDL secretion with effect on the Thus, of VLDL not lipid also on the protein that the fusion of lipid droplets with to TAG-rich a we showed that apoC-III expression could VLDL1 even under the that activity was which suggests that apoC-III may an important in second-step through an M. S. P.H. J. Wang of apolipoprotein C–III in McA-RH7777 cells VLDL and secretion under lipid-rich Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). The current to the mutation in apoC-III suggest that the mutant expression TAG the second-step VLDL maturation. and studies from and protein from brefeldin A, and from and from human apoC-III was from VLDL of or human apoC-III of in and and from was a from K. The activity of microsomal protein is accumulation of within in McA-RH7777 cells. the of very low density Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). transfected McA-RH7777 cells expressing wild-type human apoC-III or the Ala23Thr mutant was as M. S. P.H. J. Wang of apolipoprotein C–III in McA-RH7777 cells VLDL and secretion under lipid-rich Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). The cells in and C3wt and C3AT cells in with in with and or was lipid in of and which was with and in a The was by and was a and by a The with to The lumenal from with by a at The lumenal from microsomal by to cumulative rate K. The activity of microsomal protein is accumulation of within in McA-RH7777 cells. the of very low density Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). from fractions microsomal and and lumenal lipoprotein by and the associated with [3H]TAG and was by as M. S. P.H. J. Wang of apolipoprotein C–III in McA-RH7777 cells VLDL and secretion under lipid-rich Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). with and with and and by and the lumenal by with as The lumenal by cumulative rate and and from and by by associated with apolipoproteins was by In some cells treated with brefeldin the and with to of as K. The activity of microsomal protein is accumulation of within in McA-RH7777 cells. the of very low density Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, S. K. J. inhibits the of lipoproteins in McA-RH7777 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). McA-RH7777 cells expressing human and apoC-III in 1 and in L. M. L. J. Role of ADP ribosylation factor 1 in the and secretion of Thromb. Vasc. Biol. PubMed Scopus Google Scholar). The with and by the by The was to with or apoC-III The by to and apoC-III by The activity of was as M. S. P.H. J. Wang of apolipoprotein C–III in McA-RH7777 cells VLDL and secretion under lipid-rich Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). concentration was by the and the of of protein the of PubMed Scopus Google Scholar). with cells, expression of wild-type apoC-III in McA-RH7777 cells C3wt cells) the secretion of TAG or in the presence of and the effect of apoC-III in lipid secretion was by the expression of the mutant C3AT cells) The of TAG and was comparable the of cells the lipid secretion was by an in secretion from not from cells. of was not by apoC-III expression showed that expression of wild-type apoC-III in increased secretion of expression of the Ala23Thr mutant had effect with The of showed between C3AT cells and the These with what was M. S. P.H. J. Wang of apolipoprotein C–III in McA-RH7777 cells VLDL and secretion under lipid-rich Lipid Res. Full Text Full Text PDF PubMed Scopus Google that is a mutation in human apoC-III that to secretion of TAG and To determine the and TAG secretion was to TAG-rich VLDL1 we in association with lipoproteins within the microsomal studies showed that at the to associated with and the VLDL1 the second was in a K. G. J. L. J.C. of very low density lipoproteins apolipoprotein in McA-RH7777 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, K. The activity of microsomal protein is accumulation of within in McA-RH7777 cells. the of very low density Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). Thus, in the study we the cells with and to of VLDL1 within the In C3wt cells, was in the VLDL1 at and at the was not in the VLDL1 in C3AT was in lipoproteins as and at was an of associated with VLDL1 in C3AT cells at These results suggest that mutation apoC-III's to VLDL1 not with the of or We have shown that of VLDL through the to the elements of was associated with of the in the and in the K. G. J. L. J.C. of very low density lipoproteins apolipoprotein in McA-RH7777 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The in VLDL in of within the To determine the VLDL1 in C3AT cells was to the of lumenal lipid we lumenal distribution of lipid between C3wt and C3AT cells. To this we metabolic with in with fractionation at and of the TAG and between microsomal microsomal lumen and was showed that [3H]TAG in C3AT cells was increased with that in C3wt cells and that an at the of the and lumenal fractions that the of [3H]TAG at was increased in and lumen in C3AT cells. The level of in lumenal was also increased in C3AT cells in [3H]TAG was observed in C3AT cells with C3wt cells of was comparable between C3wt and C3AT cells These results suggest that C3AT cells had deficiency in TAG Further fractionation of the lumenal showed a distribution of [3H]TAG toward IDL/LDL and HDL fractions in C3AT cells at and [3H]TAG at In the [3H]TAG in IDL/LDL fractions in C3wt cells was significantly lower than that in C3AT cells concentration of in the IDL/LDL fractions was also observed in the microsomal lumen of C3AT cells secretion of [3H]TAG and was reduced in C3AT cells. of lumenal [3H]TAG and in VLDL fractions was in C3wt and C3AT cells, as secretion of VLDL K. G. J. L. J.C. of very low density lipoproteins apolipoprotein in McA-RH7777 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The increased accumulation of TAG in lumenal IDL/LDL fractions in C3AT cells, with TAG that the of Ala23Thr mutant in VLDL may a of of lumenal TAG VLDL1 maturation. a in TAG and increased activity is associated with increased TAG accumulation within the microsomal lumen A. S. triacylglycerol protein is lumenal of not associated with as well as Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. J. J.S. of the of microsomal protein in the of mice.J. Clin. Invest. 1999; PubMed Scopus Google Scholar, K. The activity of microsomal protein is accumulation of within in McA-RH7777 cells. the of very low density Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). We the in lumenal [3H]TAG accumulation in C3AT cells was also a of of the expression showed that expression was increased in C3wt cells with cells, the expression was significantly in the presence of C3AT mutant the in vitro TAG activity of was reduced in C3AT cells with C3wt cells These suggested that the in [3H]TAG accumulation within the microsomal lumen of C3AT cells was not to activity in cells. the suggest that the inability of C3AT cells to assemble VLDL1 was not to the of of lipid the the of lipid VLDL1 was to accumulation of TAG associated with IDL/LDL within the microsomal lumen in C3AT cells. The second-step the fusion of lipid droplets to VLDL is to brefeldin S. K. J. inhibits the of lipoproteins in McA-RH7777 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, activity of microsomal protein is the secretion of very low density lipoproteins apolipoprotein B from McA-RH7777 Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). We lumenal TAG distribution in cells treated with brefeldin or with brefeldin and shown of TAG-rich not was by brefeldin the of lipoproteins from VLDL to as K. The activity of microsomal protein is accumulation of within in McA-RH7777 cells. the of very low density Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google was by inhibition with brefeldin the second-step VLDL was [3H]TAG and accumulated in the microsomal lumen in the of lumenal lipid profiling in brefeldin cells is to that in C3AT cells [3H]TAG and also by inhibition the that the activity is of lipid microsomal The results suggest that the Ala23Thr mutant protein might with fusion of lipid with VLDL precursors. of human apoC-III by C.S. J. M. S. G. and of human Biol. Chem. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar) has on the of Thus, is that the mutation of by a on the To mutation apoC-III protein with we contrasted Ala23Thr mutant protein distribution lumenal lipoproteins with that of wild-type apoC-III of the lumenal that wild-type was of the lipoprotein fractions VLDL the Ala23Thr mutant protein was absent in VLDL1 and fractions accumulated in IDL/LDL fractions distribution of Ala23Thr mutant protein within the lumen with that of [3H]TAG in the cells as in that the mutant protein was associated with lipid droplets as IDL/LDL-like The presence of the mutant on the of lipid droplets may of lipid droplets showed that of apoC-III could by of the an was by Thus, between apoC-III and or within the was These results suggest that the Ala23Thr through association with may with VLDL by second-step with the that apoC-III a in second-step current study that the of Ala23Thr mutant at the of the VLDL1 to of lumenal of metabolic in with fractionation to the through which the TAG was within the cells. that the Ala23Thr mutant expression has impact on TAG the the of TAG-rich within the microsomal lumen the IDL/LDL-like These TAG-rich in the of lipid droplets within the lumen H. R. and lipid characterization of apolipoprotein lipid droplets from mouse very low density lipoprotein Biol. Chem. Full Text Full Text PDF PubMed Scopus Google might the lipid VLDL maturation. in the presence of the Ala23Thr lumenal lipid droplets to to VLDL1. we that apoC-III as a that the fusion between and the lipid We and have shown that the VLDL associated with the microsomal not in the microsomal and the of VLDL K. G. J. L. J.C. of very low density lipoproteins apolipoprotein in McA-RH7777 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, S. P. K. The microsomal protein the of apolipoprotein very low density lipoprotein in McA-RH7777 Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). apoC-III was in the microsomal lumen and not in the of the fractionation not from the current also suggest that is between and and apoC-III the apoC-III protein on the lipid droplets and We a the of apoC-III in the of lumenal lipid droplets and fusion in the second step in the The fusion not the the fusion the of apoC-III the VLDL1 apoC-III might from the lipid droplets fusion and as These have been observed M. S. P.H. J. Wang of apolipoprotein C–III in McA-RH7777 cells VLDL and secretion under lipid-rich Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). the Ala23Thr mutant to fusion in the second-step is the of in C.S. J. M. S. G. and of human Biol. Chem. 2008; Full Text Full Text PDF PubMed Scopus Google Scholar). The the of which may the observed of apoC-III to H. R. L. R. M. of the properties and lipoprotein lipase inhibition of a apolipoprotein C–III Lipid Res. Full Text Full Text PDF PubMed Google Scholar). In an the of is an of protein Moreover, is also to a of human apoC-III L. L. A. R. properties of the N-terminal of human apolipoprotein PubMed Scopus Google Scholar). is to the or of the of an an is to the The the lipid by to peptides have been in fusion as well as in in as P. L. R. of functional a study of the and of of and human apolipoprotein B 1996; PubMed Scopus Google and lipase R. T. L. J. M. in the of 1997; Full Text PDF PubMed Scopus Google protein R. T. L. J. M. in the of 1997; Full Text PDF PubMed Scopus Google A. M. J. R. M. of the of an to of association with J. PubMed Scopus Google G. A. A. J. J. R. M. The of human apolipoprotein promotes the fusion of and apolipoprotein from J. PubMed Scopus Google and J. J. M. J. of lipid by the microsomal Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In the of the has a of with the L. L. A. R. properties of the N-terminal of human apolipoprotein PubMed Scopus Google Scholar). The of apoC-III had lower and and with H. L. R. G. J. M. of and of apolipoprotein lipid of and inhibition of lipoprotein PubMed Scopus Google Scholar). These properties of the at the N-terminal region of apoC-III confer and in of the could as as may between and lipid fusion is the mutation the of this in fusion between lipid droplets and to suggest that the presence of this at the of apoC-III could as a We that expression of a that the amino of apoC-III the in secretion of the protein and Moreover, expression of the in secretion as as the apoC-III protein the and The of structural associated with human apoC-III We have the by which the mutation to the of of apoC-III in the and secretion of TAG-rich VLDL1 from cells under lipid-rich conditions. study suggests that an important structural element of human residing within the N-terminal region of this may in the fusion between lipid droplets and in the second-step VLDL1

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.