Distribution of apolipoprotein E between free and A-II complexed forms in very-low- and high-density lipoproteins: functional implications

Borghini, Isabelle; James, Richard; Blatter, Marie-Claude; Pometta, D

doi:10.1016/0005-2760(91)90034-f

Cited by 24 publications

(16 citation statements)

References 43 publications

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“…By 24 h, apo E homodimers and apo A-II-apo E heterodimers are detected and these are associated with larger HDL particles (Fractions 4 – 6), while only monomeric apo E is present in LDL Fraction 3. In human plasma also the dimeric apo E content of HDL particles is relatively high while monomeric apo E is predominantly on apo B-containing lipoproteins [29, 45]. Media apo B appeared in Fraction 1 (VLDL) and to a lesser extent in Fraction 3 (LDL) (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…At this later time, for all three apolipoproteins, a larger proportion was recovered in the lipid-free d>1.25 fraction (24 – 28%). This could be due to the low amount of lipid production by HepG2 cells [38, 30, 39, 40] and/or loss of apolipoproteins from lipoproteins during ultracentrifugation (see below) [44, 11, 45]. The minor lipid-free apo A-II monomer bands detected in 24 h media (Figure 1, Panel B, anti-A-II, lanes 7 and 8) have increased molecular weight, and may be glycosylated isoforms [46].…”

Section: Resultsmentioning

confidence: 99%

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Apolipoproteins A-I, A-II and E are independently distributed among intracellular and newly secreted HDL of human hepatoma cells

Gillard

Lin

Massey

et al. 2009

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Whereas hepatocytes secrete the major human plasma high density lipoproteins (HDL)-protein, apo A-I, as lipid-free and lipidated species, the biogenic itineraries of apo A-II and apo E are unknown. Human plasma and HepG2 cell-derived apo A-II and apo E occur as monomers, homodimers and heterodimers. Dimerization of apo A-II, which is more lipophilic than apo A-I, is catalyzed by lipid surfaces. Thus, we hypothesized that lipidation of intracellular and secreted apo A-II exceeds that of apo A-I, and once lipidated, apo A-II dimerizes. Fractionation of HepG2 cell lysate and media by size exclusion chromatography showed that intracellular apo A-II and apo E are fully lipidated and occur on nascent HDL and VLDL respectively, while only 45% of intracellular apo A-I is lipidated. Secreted apo A-II and apo E occur on small HDL and on LDL and large HDL respectively. HDL particles containing both apo A-II and apo A-I form only after secretion from both HepG2 and Huh7 hepatoma cells. Apo A-II dimerizes intracellularly while intracellular apo E is monomeric but after secretion associates with HDL and subsequently dimerizes. Thus, HDL apolipoproteins A-I, A-II and E have distinct intracellular and post-secretory pathways of hepatic lipidation and dimerization in the process of HDL formation. These early forms of HDL are expected to follow different apolipoprotein-specific pathways through plasma remodeling and reverse cholesterol transport.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Apolipoproteins A-I, A-II and E are independently distributed among intracellular and newly secreted HDL of human hepatoma cells

Gillard

Lin

Massey

et al. 2009

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…Although there are a few reports of apoAII forming complexes with apoE on VLDL (74,75), this is unlikely to be the mechanism, because we have demonstrated that placing the transgene on an apoE knockout background still results in a significant increase in VLDL triglycerides (Fig. 6).…”

Section: Discussionmentioning

confidence: 97%

Apolipoprotein AII Is a Regulator of Very Low Density Lipoprotein Metabolism and Insulin Resistance

Castellani

Nguyen

Charugundla

et al. 2008

Journal of Biological Chemistry

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Apolipoprotein AII (apoAII) transgenic (apoAIItg) mice exhibit several traits associated with the insulin resistance (IR) syndrome, including IR, obesity, and a marked hypertriglyceridemia. Because treatment of the apoAIItg mice with rosiglitazone ameliorated the IR and hypertriglyceridemia, we hypothesized that the hypertriglyceridemia was due largely to overproduction of very low density lipoprotein (VLDL) by the liver, a normal response to chronically elevated insulin and glucose. We now report in vivo and in vitro studies that indicate that hepatic fatty acid oxidation was reduced and lipogenesis increased, resulting in a 25% increase in triglyceride secretion in the apoAIItg mice. In addition, we observed that hydrolysis of triglycerides from both chylomicrons and VLDL was significantly reduced in the apoAIItg mice, further contributing to the hypertriglyceridemia. This is a direct, acute effect, because when mouse apoAII was injected into mice, plasma triglyceride concentrations were significantly increased within 4 h. VLDL from both control and apoAIItg mice contained significant amounts of apoAII, with ϳ4 times more apoAII on apoAIItg VLDL. ApoAII was shown to transfer spontaneously from high density lipoprotein (HDL) to VLDL in vitro, resulting in VLDL that was a poorer substrate for hydrolysis by lipoprotein lipase. These results indicate that one function of apoAII is to regulate the metabolism of triglyceride-rich lipoproteins, with HDL serving as a plasma reservoir of apoAII that is transferred to the triglyceride-rich lipoproteins in much the same way as VLDL and chylomicrons acquire most of their apoCs from HDL.More than 95% of plasma apolipoprotein AII (apoAII) 2 is associated with high density lipoproteins (HDLs) where it is the second most abundant protein comprising ϳ20% of the HDL total protein mass (1). Studies of the physiologic effects of apoAII have focused on reverse cholesterol transport and antioxidant functions, mechanisms through which HDLs are believed to protect against atherosclerosis (2, 3). Most but not all of these studies suggest that increased apoAII impaired both of these processes and promoted atherosclerosis (4 -8). Additional evidence for other physiologic effects of apoAII has come from genetic studies in both humans and mice, which suggest a role for apoAII in triglyceride and free fatty acid metabolism (8 -10). Subsequently, studies of genetically modified mice carrying a transgene for either human or mouse apoAII (3, 11-21), as well as apoAII knockout mice (22), confirmed a complex metabolic role for apoAII, including a rather profound effect on plasma triglyceride concentrations.Hypertriglyceridemia is an integral component of the phenotype of several disease states, including type 2 diabetes, familial combined hyperlipidemia, and the metabolic syndrome, and it is likely to be one of several contributing factors underlying the increased atherosclerosis associated with these complex diseases. Hypertriglyceridemia has been demonstrated to be an independent risk factor ...

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“…Recent genome scans from different laboratories [6] have identified a locus on 1q21-q23 chromosome which belongs to apolipoprotein A II (APOA II). Apo A II is the second most abundant protein in HDL-C, but its function is not well understood [7]. The direct effect of allele-265T/ C on triglycerides and FFA metabolism has been studied in transgenic mice.…”

Section: Introductionmentioning

confidence: 99%

APOA II genotypes frequency and their interaction with saturated fatty acids consumption on lipid profile of patients with type 2 diabetes

et al. 2016

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Distribution of apolipoprotein E between free and A-II complexed forms in very-low- and high-density lipoproteins: functional implications

Cited by 24 publications

References 43 publications

Apolipoproteins A-I, A-II and E are independently distributed among intracellular and newly secreted HDL of human hepatoma cells

Apolipoproteins A-I, A-II and E are independently distributed among intracellular and newly secreted HDL of human hepatoma cells

Apolipoprotein AII Is a Regulator of Very Low Density Lipoprotein Metabolism and Insulin Resistance

APOA II genotypes frequency and their interaction with saturated fatty acids consumption on lipid profile of patients with type 2 diabetes

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