Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3

Takahashi, Sadao; Oida, Koji; Ookubo, Minoru; Suzuki, Jinya; Kohno, Mitsuyuki; Murase, Toshio; Yamamoto, Tokuo; Nakai, Tsuguhiko

doi:10.1016/0014-5793(96)00439-5

Cited by 34 publications

(21 citation statements)

References 25 publications

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“…Structurally, the VLDL-r and apoER2 are very similar to the LDL-r and to each other; both bind apoE3 and apoE4 with similar affinities [32,33]. The VLDL-r is abundantly expressed in heart and skeletal muscle and adipose, which all actively metabolize fatty acids acquired from triglyceride-rich lipoproteins [34,35], whereas apoER2 is absent from these tissues and reported to predominate in brain, with a widespread distribution [36].…”

Section: Discussionmentioning

confidence: 99%

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

Thilakawardhana

Everett

Murdock

et al. 2005

Neurobiology of Aging

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Apolipoprotein (apo) E4 is a risk factor for Alzheimer's disease, compared to wild-type apoE3. The mechanism(s) is unknown. One possibility, demonstrated in peripheral tissue cell lines, is that apoE stimulates nitric oxide synthase (NOS) via a receptor-dependent signalling pathway and that apoE4 generates inappropriate amounts of NO compared to apoE3. Prior to biochemical investigations, we have quantified the expression of several candidate receptor genes, including low-density lipoprotein (LDL)-receptor family members and scavenger receptor class B, types I and II (SR-BI/II), as well as the three NOS isoenzymes and protein kinase B (Akt), in 38 human cell lines, of which 12 derive from brain. Expression of apoE receptor 2 (apoER2), a known signalling receptor in brain, was readily detected in SH-SY-5Yand CCF-STTG1 cells, common models of neurons and astrocytes, respectively, and was highest in H4 neuroglioma and IMR-32 neuroblastoma cells. Transcripts of the other lipoprotein receptors were widely, but variably, distributed across the different cell types. Of particular note was the predominant expression of SR-BII over SR-BI in many of the brainderived cells. As the C-terminus of SR-BII, like apoER2, contains potential SH3 signalling motifs, we suggest that in brain SR-BII functions as a signal transducer receptor.

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Section: Discussionmentioning

confidence: 99%

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

Thilakawardhana

Everett

Murdock

et al. 2005

Neurobiology of Aging

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“…In addition, the LDLR binds apoB-100 and apoE, whereas the VLDLR or apoER2 binds only apoE (Takahashi et al 1992(Takahashi et al , 1996Kim et al 1996). The phenotype of apoE has no effect on binding to the VLDLR (Bieri et al 1998), and the ligand-binding site of apoE has not been identified.…”

Section: Discussionmentioning

confidence: 99%

The important role for βVLDLs binding at the fourth cysteine of first ligand-binding domain in the low-density lipoprotein receptor

Iwasaki¹,

Takahashi

Ishihara³

et al. 2004

J Hum Genet

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The low-density lipoprotein (LDL) receptor (LDLR) is a crucial role for binding and uptaking apolipoprotein (apo) B-containing lipoproteins, such as very-low-density lipoprotein (VLDL), intermediatedensity lipoprotein (IDL), and LDL. The defect function of the LDLR causes familial hypercholesterolemia (FH), the phenotype of which is elevated plasma cholesterol and premature coronary heart disease (CHD). In the present study, we characterize the role of the cysteine residue of the ligand-binding domain of the LDLR. The mutant LDLR protein of cysteine for serine at codon 25 (25S-LDLR) was expressed in Chinese hamster ovary (CHO) cell line, ldl-A7. By Western blot analysis, the 25S-LDLR was detected with monoclonal antibody IgG-12D10, which reacts with the linker site of the LDLR but not with IgG-C7, which reacts with the NH 2 terminus of the receptor. The 25S-LDLR bound LDL similarly to the wild-type LDLR, but the rate of uptake of LDL by the mutant receptor was only about half of that by the wild-type receptor. In contrast, the 25S-LDLR bound and internalized b VLDL more avidly than LDL. These results suggest that the fourth cysteine residue of the first ligand-binding domain of the LDLR might be important for the internalization of atherogenic lipoproteins by vascular cells despite reduced LDL uptake, leading to atherosclerosis and premature cardiovascular disease.Keywords Familial hypercholesterolemia AE Low-density lipoprotein receptor AE Mutation AE Ischemic heart disease AE Atherosclerosis Abbreviations FH Familial hypercholesterolemia AE LDL Low-density lipoprotein AE VLDL Very-lowdensity lipoprotein AE LDLR Low-density lipoprotein receptor AE VR Very-low-density lipoprotein receptor AE ER2 Apolipoprotein E receptor 2 AE IHD Ischemic heart disease AE DiI 3,3¢-Dioctadecylindocarbocyanine iodide

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“…Indeed, this constitutes the first report of apoER2 protein being identified in vascular endothelial cells in non-neuronal tissues. A role for apoER2 is also suggested by the similar efficacy of apoE2 and apoE3; apoE2 binds poorly to the LDL-R and LDL-R-related protein, thereby discounting them in inhibiting VCAM-1, whereas apoER2 and its closest mammalian homolog, the very-low-density receptor (VLDL-R), bind both isoforms efficiently (5,20,37). Also relevant is the proposal that both apoER2 and VLDL-R initiate tyrosine kinase signaling to modulate neuronal positioning in brain development (38), a process dependent on neuronal cell adhesion molecules (39,40).…”

Section: Fig 6 Apoer2 Is Expressed In Huvecsmentioning

confidence: 99%

Cell-derived Apolipoprotein E (ApoE) Particles Inhibit Vascular Cell Adhesion Molecule-1 (VCAM-1) Expression in Human Endothelial Cells

Stannard¹,

Riddell²,

Sacre³

et al. 2001

Journal of Biological Chemistry

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Sub-endothelial infiltration of monocytes occurs early in atherogenesis and is facilitated by cell adhesion molecules that are up-regulated on activated endothelium. Apolipoprotein E (apoE) helps protect against atherosclerosis, in part, because apoE particles secreted by macrophages have local beneficial effects at lesion sites. Here, we hypothesize that such protection includes antiinflammatory actions and investigate whether cell-derived apoE can inhibit tumor necrosis factor-␣-mediated up-regulation of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Two models were used to mimic endothelial exposure to macrophage-derived apoE. In the first, HUVECs were transiently transfected to secrete apoE; VCAM-1 induction inversely correlated with secretion of apoE into the media (r ‫؍‬ ؊0.76, p < 0.001). In the second, incubation of HUVECs with media from recombinant Chinese hamster ovary (CHO) cells expressing apoE (CHO apoE ) also reduced VCAM-1 in a dose-dependent manner (r ‫؍‬ ؊0.70, p < 0.001). Characterization of CHO apoE cell-derived apoE revealed several similarities to apoE particles secreted by human blood monocyte-derived macrophages. The suppression of endothelial activation by apoE most likely occurs via stimulation of endothelial nitric oxide synthase; apoE increased levels of intracellular nitric oxide and its surrogate marker, cyclic guanosine monophosphate, while the nitric oxide synthase inhibitor, ethylisothiourea, blocked its effect. We propose that apoE secreted locally at lesion sites by macrophages may be anti-inflammatory by stimulating endothelium to release NO and suppress VCAM-1 expression.

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Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3

Cited by 34 publications

References 25 publications

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

The important role for βVLDLs binding at the fourth cysteine of first ligand-binding domain in the low-density lipoprotein receptor

Cell-derived Apolipoprotein E (ApoE) Particles Inhibit Vascular Cell Adhesion Molecule-1 (VCAM-1) Expression in Human Endothelial Cells

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