Lysophosphatidylcholine increases apolipoprotein B secretion by enhancing lipid synthesis and decreasing its intracellular degradation in HepG2 cells

Zhou, Zhangyin; Luchoomun, Jayraz; Bakillah, Ahmed; Hussain, M. Mahmood

doi:10.1016/s0005-2760(97)00200-2

Cited by 15 publications

(14 citation statements)

References 59 publications

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“…This conclusion is supported by data showing ‫ف‬ 40% decrease in hepatic VLDL production in Pla2g1b Ϫ / Ϫ mice compared with Pla2g1b +/+ mice upon short-term hypercaloric diet feeding, prior to any observed synthesis. Lysophospholipids may also provide additional substrates to promote both triglyceride and phospholipid synthesis in hepatocytes ( 32 ), thus decreasing intracellular degradation of apoB and facilitating VLDL secretion ( 33 ). Our in vivo data are consistent with the in vitro observations that reducing LPC levels limits substrate availability of VLDL synthesis and secretion.…”

Section: Discussionsupporting

confidence: 87%

Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in mice

Hollie

Hui

2011

Journal of Lipid Research

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Section: Discussionsupporting

confidence: 87%

Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in mice

Hollie

Hui

2011

Journal of Lipid Research

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“…We previously showed that LysoPC specifically increased apoB secretion without affecting apoA-I secretion in HepG2 cells (28). However, we did not know the mechanism for this effect at that time.…”

Section: Discussionmentioning

confidence: 84%

“…The above results indicated that LPCAT3 deficiency could influence VLDL secretion through MTP. More than 10 years ago we showed that LysoPC increased triglyceride-rich particle secretion in HepG2 cells (28), but at that time we did not evaluate the effect of LysoPC on MTP. Therefore, we hypothesized that LPCAT3 knockdown-mediated LysoPC accumulation in hepatocyte may up-regulate MTP expression and promote assembly and secretion of triglyceride-rich apoB particle.…”

Section: Impact Of Lpcat3 Knockdown On Hepatic and Plasma Lipidmentioning

confidence: 99%

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Lysophosphatidylcholine Acyltransferase 3 Knockdown-mediated Liver Lysophosphatidylcholine Accumulation Promotes Very Low Density Lipoprotein Production by Enhancing Microsomal Triglyceride Transfer Protein Expression

Ding

Pan

et al. 2012

Journal of Biological Chemistry

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“…Purified human apoA-I (100 mg/2 ml) was incubated with or without vesicles and subjected to ultracentrifugation. Fractions were collected from the top of the tube, and apoA-I was measured by ELISA (52,53) …”

Section: Modulation Of Protein-protein Interactions By Lipids-mtpmentioning

confidence: 99%

Binding of Microsomal Triglyceride Transfer Protein to Lipids Results in Increased Affinity for Apolipoprotein B

Bakillah¹,

Hussain²

2001

Journal of Biological Chemistry

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Apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) are known to interact with each other. We evaluated the effect of different lipids on the protein-protein interactions between MTP and apoB100 or its C-terminally truncated forms. Negatively charged lipids decreased protein-protein interactions between apoB and MTP. In contrast, zwitterionic phospholipids enhanced (2-4-fold) the binding of apoB100 to MTP by increasing affinity (1.5-3-fold) between these proteins without affecting the number of binding sites. Similarly, phospholipids augmented (1.5-4-fold) the binding of various C-terminally truncated apoB peptides to MTP. The increased binding was greater for apoB peptides containing lipidbinding domains, such as apoB28 and apoB42. Surprisingly, preincubation of apoB28 with lipid vesicles had no effect on MTP binding. In contrast, incubation of MTP with lipid vesicles resulted in a stable association of MTP with vesicles, and MTP-lipid vesicles bound better (5-fold increase) to LDL than did lipid-free MTP. To determine whether MTP exists stably associated with lipids in cells, microsomal contents from COS cells expressing MTP, HepG2 cells, and mouse liver were ultracentrifuged, and MTP was visualized in different density fractions. MTP was found associated and unassociated with lipids. In contrast, apoB17 and apoB:270 -570 were present unassociated with lipids in COS cells. These studies show that the binding of MTP to lipids results in increased affinity for apoB and that stable MTP-lipid complexes exist in the lumen of the endoplasmic reticulum. Protein-protein interactions between apoB and MTP may juxtapose lipids associated with MTP to lipid-binding domains of apoB and facilitate hydrophobic interactions leading to enhance affinity. We speculate that MTP-lipid complexes may serve as nuclei to form "primordial lipoproteins" and may also play a role in the bulk addition of lipids during the "core expansion" of these lipoproteins. Apolipoprotein B (apoB)1 is essential for the transport of lipids packaged into lipid-protein complexes called lipoproteins. Assembly of these lipoproteins requires, in addition to apoB, microsomal triglyceride transfer protein (MTP). In vitro kinetic studies suggest that MTP may catalyze transfer of lipids between vesicles by a shuttle mechanism (1). In this process, each MTP molecule is proposed to interact transiently with donor vesicles, extract up to 2 mol of PC and 0.25 mol of triglycerides, dissociate from these vesicles, interact transiently with acceptor vesicles, and rapidly deliver lipid molecules to these vesicles (1, 2). The importance of this lipid transfer activity in lipoprotein assembly was established by identifying mutations in MTP gene that result in loss of lipid transfer activity in patients that lack apoB-containing lipoproteins in their plasma (3-5), by identifying compounds that inhibit in vitro lipid transfer activity and decrease apoB secretion (6 -9), and by manipulating gene expression and correlating it to changes in apoB secretion...

show abstract

Lysophosphatidylcholine increases apolipoprotein B secretion by enhancing lipid synthesis and decreasing its intracellular degradation in HepG2 cells

Cited by 15 publications

References 59 publications

Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in mice

Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in mice

Lysophosphatidylcholine Acyltransferase 3 Knockdown-mediated Liver Lysophosphatidylcholine Accumulation Promotes Very Low Density Lipoprotein Production by Enhancing Microsomal Triglyceride Transfer Protein Expression

Binding of Microsomal Triglyceride Transfer Protein to Lipids Results in Increased Affinity for Apolipoprotein B

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