Carboxyl Terminus of Apolipoprotein A-I (ApoA-I) Is Necessary for the Transport of Lipid-free ApoA-I but Not Prelipidated ApoA-I Particles through Aortic Endothelial Cells

Ohnsorg, Pascale M.; Rohrer, Lucia; Perisa, Damir; Kateifides, Andreas; Chroni, Angeliki; Kardassis, Dimitris; Zannis, Vassilis I.; Eckardstein, Arnold von

doi:10.1074/jbc.m110.193524

Cited by 28 publications

(35 citation statements)

References 45 publications

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“…8 In addition, we showed that the transendothelial apoA-I transport is a 2-step process in which apoA-I is initially lipidated by ABCA1 and then further processed by ABCA1-independent mechanisms, most likely involving ABCG1 and SR-BI. 9 In the present study, we provide strong biochemical evidence that apoA-I stimulates the transport of initially lipid-free apoA-I and HDL across endothelial cells by inducing ectopic cell surface F 0 F 1 ATPase to generate extracellular ADP, which then stimulates the endocytosis of HDL or lipidated apoA-I by activating the purinergic receptor P2Y 12 ( Figure 6). F 0 F 1 ATPase is the principal ATP synthesis complex in mitochondria.…”

Section: Discussionmentioning

confidence: 90%

The β-Chain of Cell Surface F ₀ F ₁ ATPase Modulates ApoA-I and HDL Transcytosis Through Aortic Endothelial Cells

Cavelier

Ohnsorg

Rohrer

et al. 2012

ATVB

Self Cite

104

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Objective-Both HDLs and their major protein constituent apolipoprotein A-I (apoA-I) are transported through aortic endothelial cells. The knock-down of the ATP-binding cassette transporters A1 (ABCA1), G1 (ABCG1), and of the scavenger receptor-BI (SR-BI) diminishes but does not completely block the transport of apoA-I or HDL, so that other receptors appear to be involved. The ectopic ␤-chain of F 0 F 1 ATPase has been previously characterized as an apoA-I receptor, triggering HDL internalization in hepatocytes. Methods and Results-The ectopic presence of the ␤-chain of F 0 F 1 ATPase on the surface of endothelial cells was confirmed by cell surface biotinylation. RNA-interference and the F 0 F 1 ATPase inhibitory peptide IF 1 reduced cell binding of apoA-I but not HDL, as well as association and transendothelial transport of both apoA-I and HDL. Furthermore, apoA-I stimulated F 0 F 1 ATPase catalyzed ATP hydrolysis. The generated ADP as well as apoA-I stimulated the binding, cell association, and internalization of HDL. Both in the presence and absence of ADP inhibition of the purinergic receptor P2Y 12 but not P2Y 1 decreased the cell association of apoA-I and HDL. Coinhibition of ␤-ATPase and ABCA1 had no additive effects on the cell association and transport of apoA-I. Reduced cell association of HDL by ␤-ATPase inhibition was not further decreased by additional knock-down of ABCG1 or SR-BI. Conclusion-Binding of apoA-I to ectopic F 0 F 1 ATPase triggers the generation of ADP, which via activation of the purinergic receptor P2Y 12 stimulates the uptake and transport of HDL and initially lipid-free apoA-I by endothelial cells. Key Words: apolipoproteins Ⅲ endothelium Ⅲ lipoproteins Ⅲ F0F1 ATPase Ⅲ transcytosis P lasma levels of HDL cholesterol as well as apolipoprotein A-I (apoA-I) are inversely correlated with the risk of atherosclerosis. In addition, both apoA-I and HDL exert several atheroprotective properties within the arterial wall rather than in the blood stream, including cholesterol efflux from macrophage foam cells. 1 HDLs are indeed the most abundant lipoproteins in the extravascular space. 2-5 Recently, we provided evidence that endothelial cells bind, internalize, and transcytose apoA-I and HDL in a saturable and temperature-dependent manner. 6 By siRNA interference we also showed that the ATP-binding cassette transporter (ABC) A1 modulates endothelial transport of apoA-I, 7 whereas ABCG1 and the scavenger receptor BI (SR-BI) modulate the transport of HDL. 8 In addition, we showed that the transendothelial apoA-I transport is a 2-step process in which apoA-I is initially lipidated by ABCA1 and then further processed by mechanisms that are independent of ABCA1 but involve Previously, the ectopically expressed ␤-chain of F 0 F 1 ATPase (␤-ATPase) has been identified as a hepatic receptor for apoA-I. 10 F 0 F 1 ATPase is an enzymatic complex responsible for the synthesis of ATP in mitochondria, prokaryote membranes, and chloroplasts. The mitochondrial F 0 F 1 ATPase (about 600 kDa) is composed of 2 ...

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Section: Discussionmentioning

confidence: 90%

The β-Chain of Cell Surface F ₀ F ₁ ATPase Modulates ApoA-I and HDL Transcytosis Through Aortic Endothelial Cells

Cavelier

Ohnsorg

Rohrer

et al. 2012

ATVB

Self Cite

104

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“…Together with lipocalin, apoA-I has been suggested as a potential biomarker for chronic obstructive pulmonary disease (Nicholas et al 2010). The origin of apoA-I in fluids of the airways has not been extensively studied, but trans-endothelial transport has been investigated (Ohnsorg et al 2011). The presence, composition and possible function of apoA-I containing lipoprotein particles in external fluids remain to be investigated.…”

Section: Detoxification Of Plasma and External Fluidsmentioning

confidence: 99%

Functionality of HDL: Antioxidation and Detoxifying Effects

Karlsson

Kontush

James

2014

Handbook of Experimental Pharmacology

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“…Human HDL was isolated from plasma of healthy blood donors (Kantosspital Schaffhausen, Switzerland) or mouse plasma by stepwise ultracentrifugation (d = 1.063-1.21 kg/l) at 360,000 g for 15 h at 15°C, as described previously ( 24 ), using solid potassium bromide (Sigma Aldrich, Buchs, Switzerland) for density adjustment. apoA-I was further purifi ed from delipidated HDL as described previously ( 24 ).…”

Section: Isolation and Reconstitution Of Hdlmentioning

confidence: 99%

“…apoA-I was further purifi ed from delipidated HDL as described previously ( 24 ). Discoidal reconstituted HDL (rHDL) particles were produced by the cholate dialysis method and contained apoA-I , POPC (Sigma), and sodium cholate (Sigma) in a molar ratio of 1/100/100 ( 24 ).…”

Section: Isolation and Reconstitution Of Hdlmentioning

confidence: 99%

Apolipoprotein M modulates erythrocyte efflux and tubular reabsorption of sphingosine-1-phosphate

Sutter

Park

Othman

et al. 2014

Journal of Lipid Research

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This article is available online at http://www.jlr.org Supplementary key words high density lipoprotein • kidney • megalin • chloride-proton exchanger ClC5 • cystinosin Sphingosine-1-phosphate (S1P) acts both as an intracellular signaling molecule and an extracellular agonist of at least fi ve different G protein-coupled receptors. By its dual functions, S1P regulates the survival, proliferation, and migration as well as the functionality of many cells, eventually in opposite directions ( 1-4 ). Therefore the absolute and relative abundance of S1P in intracellular and extracellular compartments appears to be important for its biological functionality ( 4 ).Most cells form S1P by the phosphorylation of sphingosine, a degradation product of ceramides, through sphingosine kinase and degrade S1P to phosphoethanolamine and fatty aldehyde through S1P-lyase ( 1-4 ). By contrast, not only erythrocytes and platelets, but also other cells which have low or no lyase activity, release S1P ( 4-6 ), probably by an as yet unidentifi ed ABC transporter ( 4,7,8 ). Within the plasma compartment, the majority of S1P is transported by HDLs in which it exerts many cyto-protective and anti-infl ammatory effects, for example, on endothelial cells ( 8-10 ). The enrichment of S1P in HDL has been explained by the presence of a specifi c S1P binding protein, namely apoM ( 10 ). Purifi ed and recombinant apoM binds S1P with an IC 50 of 0.9 mol/l, which is in the range of physiological S1P plasma concentrations ( 11 ). X-ray crystallography of apoM identifi ed an S1P binding domain which was confi rmed by the recombinant generation of non-S1P binding apoM mutants ( 11 ). In agreement with these physicochemical data, S1P was copurifi ed with apoM containing HDL, but not apoM-free HDL, from both human Abstract Sphingosine-1-phosphate (S1P) mediates several cytoprotective functions of HDL. apoM acts as a S1P binding protein in HDL. Erythrocytes are the major source of S1P in plasma. After glomerular fi ltration, apoM is endocytosed in the proximal renal tubules. Human or murine HDL elicited time-and dose-dependent S1P effl ux from erythrocytes. Compared with HDL of wild-type (wt) mice, S1P effl ux was enhanced in the presence of HDL from apoM transgenic mice, but not diminished in the presence of HDL from apoM knockout ( Apom ؊ / ؊ ) mice. Artifi cially reconstituted and apoM-free HDL also effectively induced S1P effl ux from erythrocytes. S1P and apoM were not measurable in the urine of wt mice. Apom ؊ / ؊ mice excreted signifi cant amounts of S1P. apoM was detected in the urine of mice with defective tubular endocytosis because of knockout of the LDL receptor-related protein, chloride-proton exchanger ClC-5 ( Clcn5 ؊ / ؊ ), or the cysteine transporter cystinosin. Urinary levels of S1P were signifi cantly elevated in Clcn5 ؊ / ؊ mice. In contrast to Apom ؊ / ؊ mice, these mice showed normal plasma concentrations for apoM and S1P. In conclusion, HDL facilitates S1P effl ux from erythrocytes by both apoMdependent and apoM-independent mechanisms...

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Carboxyl Terminus of Apolipoprotein A-I (ApoA-I) Is Necessary for the Transport of Lipid-free ApoA-I but Not Prelipidated ApoA-I Particles through Aortic Endothelial Cells

Cited by 28 publications

References 45 publications

The β-Chain of Cell Surface F ₀ F ₁ ATPase Modulates ApoA-I and HDL Transcytosis Through Aortic Endothelial Cells

The β-Chain of Cell Surface F ₀ F ₁ ATPase Modulates ApoA-I and HDL Transcytosis Through Aortic Endothelial Cells

Functionality of HDL: Antioxidation and Detoxifying Effects

Apolipoprotein M modulates erythrocyte efflux and tubular reabsorption of sphingosine-1-phosphate

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Carboxyl Terminus of Apolipoprotein A-I (ApoA-I) Is Necessary for the Transport of Lipid-free ApoA-I but Not Prelipidated ApoA-I Particles through Aortic Endothelial Cells

Cited by 28 publications

References 45 publications

The β-Chain of Cell Surface F 0 F 1 ATPase Modulates ApoA-I and HDL Transcytosis Through Aortic Endothelial Cells

The β-Chain of Cell Surface F 0 F 1 ATPase Modulates ApoA-I and HDL Transcytosis Through Aortic Endothelial Cells

Functionality of HDL: Antioxidation and Detoxifying Effects

Apolipoprotein M modulates erythrocyte efflux and tubular reabsorption of sphingosine-1-phosphate

Contact Info

Product

Resources

About

The β-Chain of Cell Surface F ₀ F ₁ ATPase Modulates ApoA-I and HDL Transcytosis Through Aortic Endothelial Cells

The β-Chain of Cell Surface F ₀ F ₁ ATPase Modulates ApoA-I and HDL Transcytosis Through Aortic Endothelial Cells