Apolipoprotein binding to protruding membrane domains during removal of excess cellular cholesterol

Lin, Guorong; Oram, John F.

doi:10.1016/s0021-9150(99)00503-1

Cited by 61 publications

(51 citation statements)

References 54 publications

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“…46 and references contained therein), and as expected from the reaction scheme (Fig. 1), apo E has been shown to bind to the exovesiculated domains created by ABCA1 activity (23).…”

Section: Resultssupporting

confidence: 60%

“…Immunogold Labeling and Electron Microscopy-Immunogold labeling of J774 cells was performed essentially as described previously (23). Briefly, J774 cells in which ABCA1 was up-regulated with cAMP and control cells were incubated with apo A-I (10 g/ml) at 37°C for 4 h, after which they were washed with phosphate-buffered saline and prefixed with paraformaldehyde (4%) in phosphate-buffered saline (pH 7.4) for 30 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

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Mechanism of ATP-binding Cassette Transporter A1-mediated Cellular Lipid Efflux to Apolipoprotein A-I and Formation of High Density Lipoprotein Particles

Vedhachalam

Duong

Nickel

et al. 2007

Journal of Biological Chemistry

305

310

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The ATP-binding cassette transporter A1 (ABCA1) plays a critical role in the biogenesis of high density lipoprotein (HDL) particles and in mediating cellular cholesterol efflux. The mechanism by which ABCA1 achieves these effects is not established, despite extensive investigation. Here, we present a model that explains the essential features, especially the effects of ABCA1 activity in inducing apolipoprotein (apo) A-I binding to cells and the compositions of the discoidal HDL particles that are produced. The apo A-I/ABCA1 reaction scheme involves three steps. First, there is binding of a small regulatory pool of apo A-I to ABCA1, thereby enhancing net phospholipid translocation to the plasma membrane exofacial leaflet; this leads to unequal lateral packing densities in the two leaflets of the phospholipid bilayer. Second, the resultant membrane strain is relieved by bending and by creation of exovesiculated lipid domains. The formation of highly curved membrane surface promotes high affinity binding of apo A-I to these domains. Third, this pool of bound apo A-I spontaneously solubilizes the exovesiculated domain to create discoidal nascent HDL particles. These particles contain two, three, or four molecules of apo A-I and a complement of membrane phospholipid classes together with some cholesterol. A key feature of this mechanism is that membrane bending induced by ABCA1 lipid translocase activity creates the conditions required for nascent HDL assembly by apo A-I. Overall, this mechanism is consistent with the known properties of ABCA1 and apo A-I and reconciles many of the apparently discrepant findings in the literature.

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“…46 and references contained therein), and as expected from the reaction scheme (Fig. 1), apo E has been shown to bind to the exovesiculated domains created by ABCA1 activity (23).…”

Section: Resultssupporting

confidence: 60%

Section: Methodsmentioning

confidence: 99%

Mechanism of ATP-binding Cassette Transporter A1-mediated Cellular Lipid Efflux to Apolipoprotein A-I and Formation of High Density Lipoprotein Particles

Vedhachalam

Duong

Nickel

et al. 2007

Journal of Biological Chemistry

305

310

View full text Add to dashboard Cite

show abstract

“…9A ) ( 39 ). Those domains bend from the plasma membrane to relieve the strain in the densely packed phospholipids ( 21,46 ), exposing the interact with ABCA1. The extent of this damage could not be assessed from total apoA-I isolated from atherosclerosis lesions, because most of the lesion apoA-I colocalizes with proteoglycans in noncellular regions ( 51 ).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in addition to impairing lipid removal, chlorination of apoA-I reduces its ability to stimulate JAK2 signaling. The majority of apoA-I binding sites on the surfaces of cells that express ABCA1 appear to be lipid domains formed by ABCA1 through exofacially directed transport of phospholipids to the outer plasma membrane ( 19,21,22,46 ). We therefore determined how oxidation by the MPO pathway affected the ability of apoA-I to bind to such cells.…”

Section: Phospholipid Binding Of Apoa-imentioning

confidence: 99%

Oxidation of apolipoprotein A-I by myeloperoxidase impairs the initial interactions with ABCA1 required for signaling and cholesterol export

Shao

Tang

Heinecke

et al. 2010

Journal of Lipid Research

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Population studies have shown an inverse relationship between plasma HDL levels and the risk for atherosclerotic disease, implying that factors associated with HDL metabolism are cardioprotective. HDL and its major protein, apolipoprotein A-I (apoA-I), are thought to protect against atherosclerosis by several diverse mechanisms, including removing excess cholesterol from arterial macrophages, reducing infl ammation, and inhibiting lipoprotein oxidation ( 1 ). There is strong evidence that the infl ammatory milieu of atherosclerotic tissue can promote oxidation of HDL apolipoproteins and impair their cardioprotective activities ( 2 ).One oxidative pathway in the human artery wall involves myeloperoxidase (MPO), a phagocyte heme protein that colocalizes with arterial macrophages ( 3, 4 ). MPO uses hydrogen peroxide (H 2 O 2 ) and chloride to generate hypochlorous acid (HOCl), a powerful chlorinating oxidant ( 5 ). MPO also uses H 2 O 2 and nitrite (NO 2 Ϫ ) to generate reactive species that nitrate proteins ( 6, 7 ). HDL isolated from human atherosclerotic lesions contains high levels of 3-chlorotyrosine and 3-nitrotyrosine ( 8-10 ). In mouse models of acute infl ammation, generation of both of these oxidized amino acids is markedly impaired when the mice are defi cient in MPO ( 7, 11 ). Moreover, levels of 3-chlorotyrosine and 3-nitrotyrosine are markedly higher in HDL isolated from plasma of subjects with established coronary artery disease than in HDL from healthy subjects ( 8-10 ). These fi ndings indicate that MPO targets HDL for oxidation in humans and support the concept that reactions Abstract A key cardioprotective effect of high-density lipoprotein involves the interaction of its major protein, apolipoprotein A-I (apoA-I) with ATP-binding cassette transporter A1 (ABCA1), a macrophage cholesterol exporter. ApoA-I is thought to remove cholesterol from macrophages by a cascade of events. First it binds directly to ABCA1, activating signaling pathways, and then it binds to and solubilizes lipid domains generated by ABCA1. HDL isolated from human atherosclerotic lesions and blood of subjects with established coronary artery disease contains elevated levels of 3-chlorotyrosine and 3-nitrotyrosine, two characteristic products of myeloperoxidase (MPO), a heme protein secreted by macrophages. Here we show that chlorination (but not nitration) of apoA-I by the MPO pathway impairs its ability to interact directly with ABCA1, to activate the Janus kinase 2 signaling pathway, and to promote effl ux of cellular cholesterol. In contrast, oxidation of apoA-I has little effect on its ability to stabilize ABCA1 protein or to solubilize phospholipids. Our results indicate that chlorination of apoA-I by the MPO pathway selectively inhibits two critical early events in cholesterol effl ux: (1) the binding of apoA-I to ABCA1 and (2) the activation of a key signaling pathway. Therefore, oxidation of apoA-I in the artery wall by MPO-generated chlorinating intermediates may contribute to atherogenesis by impairing cholesterol ef...

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“…The third model suggests the binding between apoA-I and ABCA1 constitutively generate cholesterol-and phospholipidrich membrane domains (89). These domains bend from the plasma membrane to relieve the strain of the densely packed phospholipids, generating curved and disordered lipid surfaces that favor apoA-I interactions (90,91) (Figure 2C). This model also has been action so that we can uncover novel therapeutic targets for treating interrelated diseases.…”

Section: Influencing Factors For the Binding Between Apoa-i And Abca1mentioning

confidence: 99%

The Interaction of ApoA-I and ABCA1 Triggers Signal Transduction Pathways to Mediate Efflux of Cellular Lipids

Zhao

Yin

et al. 2011

Mol Med

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Reverse cholesterol transport (RCT) has been characterized as a crucial step for antiatherosclerosis, which is initiated by ATPbinding cassette A1 (ABCA1) to mediate the efflux of cellular phospholipids and cholesterol to lipid-free apolipoprotein A-I (apoA-I). However, the mechanisms underlying apoA-I/ABCA1 interaction to lead to the lipidation of apoA-I are poorly understood. There are several models proposed for the interaction of apoA-I with ABCA1 as well as the lipidation of apoA-I mediated by ABCA1. ApoA-I increases the levels of ABCA1 protein markedly. In turn, ABCA1 can stabilize apoA-I. The interaction of apoA-I with ABCA1 could activate signaling molecules that modulate posttranslational ABCA1 activity or lipid transport activity. The key signaling molecules in these processes include protein kinase A (PKA), protein kinase C (PKC), Janus kinase 2 (JAK2), Rho GTPases and Ca 2+ , and many factors also could influence the interaction of apoA-I with ABCA1. This review will summarize these mechanisms for the apoA-I interaction with ABCA1 as well as the signal transduction pathways involved in these processes.

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Apolipoprotein binding to protruding membrane domains during removal of excess cellular cholesterol

Cited by 61 publications

References 54 publications

Mechanism of ATP-binding Cassette Transporter A1-mediated Cellular Lipid Efflux to Apolipoprotein A-I and Formation of High Density Lipoprotein Particles

Mechanism of ATP-binding Cassette Transporter A1-mediated Cellular Lipid Efflux to Apolipoprotein A-I and Formation of High Density Lipoprotein Particles

Oxidation of apolipoprotein A-I by myeloperoxidase impairs the initial interactions with ABCA1 required for signaling and cholesterol export

The Interaction of ApoA-I and ABCA1 Triggers Signal Transduction Pathways to Mediate Efflux of Cellular Lipids

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