Apolipoprotein-mediated cellular cholesterol/phospholipid efflux and plasma high density lipoprotein level in mice

Tsujita, Maki; Tomimoto, Shigehiro; Okumura-Noji, Kuniko; Okazaki, Mitsuyo; Yokoyama, Shinji

doi:10.1016/s1388-1981(00)00061-5

Cited by 40 publications

(36 citation statements)

References 51 publications

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“…Consistent with our previous reports (23,24), probucol inhibited the apoA-I-mediated cellular lipid release (Fig. 1A).…”

Section: Resultssupporting

confidence: 93%

“…However, probucol substantially reduces plasma HDL (22). We reported that probucol causes dramatic selective inhibition of the apolipoprotein-mediated cellular lipid release and its binding to cells (23) to cause reduction of HDL (24), which is analogous to the finding with Tangier disease (3,4). Thus, this is another piece of evidence that the apolipoprotein-cell interaction to generate HDL is a major source of plasma HDL.…”

mentioning

confidence: 54%

“…We further investigated an in vivo effect of probucol by using mouse models. Probucol inhibited the production of HDL in mice, and the kinetic analysis of plasma HDL revealed the enhanced clearance of HDL apoprotein by probucol but no difference in the HDL-lipid clearance (24), an exact analogy to the behavior of HDL in Tangier disease patients (47), indicating that probucol inhibits the reaction to generate HDL that is lacking in patients with Tangier disease. The use of probucol in the lecithin:cholesterol acyltransferase-deficient mice showed that cholesterol accumulated only in the liver, suggesting that the liver is the major organ where generation of HDL by this mechanism takes place (48).…”

Section: Discussionmentioning

confidence: 94%

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Probucol Inactivates ABCA1 in the Plasma Membrane with Respect to Its Mediation of Apolipoprotein Binding and High Density Lipoprotein Assembly and to Its Proteolytic Degradation

Chengai

Tsujita

Hayashi

et al. 2004

Journal of Biological Chemistry

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Probucol has been shown to inhibit the release of cellular lipid by helical apolipoprotein and thereby to reduce plasma high density lipoprotein. We attempted to explore the underlying mechanism for this effect in human fibroblast WI-38. Probucol inhibited the apoA-Imediated cellular lipid release and binding of apoA-I to the cells in a dose-dependent manner. It did not influence cellular uptake of low density lipoprotein, transport of cholesterol to the cell surface whether de novo synthesized or delivered as low density lipoprotein, and overall cellular content of cholesterol, although biosynthesis of lipids from acetate was somewhat increased. Probucol did not affect the mRNA level of ABCA1, and ABCA1 was recovered along with marker proteins for plasma membrane regardless of the presence of probucol. However, the protein level of ABCA1 increased, and the rate of its decay in the presence of cycloheximide was slower in the probucol-treated cells. ABCA1 in the probucol-treated cells was resistant to digestion by calpain but not by trypsin. We concluded that probucol inactivates ABCA1 in the plasma membrane with respect to its function in mediating binding of and lipid release by apolipoprotein and with respect to proteolytic degradation by calpain.Cholesterol is an essential molecule for animal cells to maintain and regulate function and structure of the biomembrane. It is synthesized in most somatic cells, whereas its catabolic site is limited to the liver and to the steroidogenic cells except for partial hydroxylation in some somatic cells. Accordingly, cholesterol is removed from the cells and transported to the liver for its conversion to bile acids, and this is one of the essential events in cholesterol homeostasis for the body and for the cells (1). High density lipoprotein (HDL) 1 is believed to play a central role in this system, and this is thought to be one of the antiatherogenic characteristics of HDL. This reaction takes place through at least two distinct mechanisms: 1) physicochemical release of cholesterol from the cell surface, which is driven by cholesterol esterification on HDL, and 2) the apolipoprotein-mediated pathway to remove cellular cholesterol and phospholipid to generate new HDL particles (2). HDL thus plays a central role in both mechanisms.Apolipoprotein-dependent cellular cholesterol release is absent in fibroblasts from patients with Tangier disease (3, 4), and mutations in the gene encoding the ATP-binding cassette transporter A1 (ABCA1) are the underlying cause of this disease (5-9). On the other hand, in vitro overexpression of functional ABCA1 in the cells (10, 11) and induction of ABCA1 expression by cyclic AMP analogues (12, 13) or by the ligands for the liver X receptor or retinoid X receptor (14, 15) enhanced the release of cellular cholesterol and phospholipid by apolipoprotein. The transgenic mice for ABCA1 had a significant increase in plasma HDL (16,17). These results indicate that this protein is a regulating factor for the plasma HDL level through generation of HDL b...

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“…Consistent with our previous reports (23,24), probucol inhibited the apoA-I-mediated cellular lipid release (Fig. 1A).…”

Section: Resultssupporting

confidence: 93%

mentioning

confidence: 54%

Section: Discussionmentioning

confidence: 94%

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Probucol Inactivates ABCA1 in the Plasma Membrane with Respect to Its Mediation of Apolipoprotein Binding and High Density Lipoprotein Assembly and to Its Proteolytic Degradation

Chengai

Tsujita

Hayashi

et al. 2004

Journal of Biological Chemistry

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“…ABCA1 plays a key role in this reaction, shown by defect of apolipoprotein-mediated cellular lipid release and the disappearance of plasma HDL in familial HDL deficiencies caused by its mutations (2-6), in ABCA1 knockout mice (7,8), WHAM chicken (33), and probucol treatment (34,35). The increase of ABCA1 expression results in enhancement of the apolipoprotein-mediated HDL production by cells in vitro and an increase of plasma HDL in vivo (9 -15).…”

Section: Fig 3 Pkc Regulates Apoa-i-induced Stabilization Of Abca1mentioning

confidence: 99%

Apolipoprotein A-I Activates Protein Kinase Cα Signaling to Phosphorylate and Stabilize ATP Binding Cassette Transporter A1 for the High Density Lipoprotein Assembly

Yamauchi

Hayashi

Abe-Dohmae

et al. 2003

Journal of Biological Chemistry

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129

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“…Fibroblasts from patients with a genetic defect of plasma HDL lack the interaction with apolipoprotein, indicating that this reaction is a main source of plasma HDL (5,6). This view is supported by the finding that probucol, which markedly reduces plasma HDL, blocks the cell-apolipoprotein interaction (7)(8)(9). Mutations were identified in ATP-binding cassette transporter (ABC) A1 with many HDL-deficient families (10 -12), so that this protein is considered as a key for generation of HDL by the apolipoprotein-cell interaction and release of cellular cholesterol by this pathway.…”

mentioning

confidence: 99%

Helical Apolipoproteins Stabilize ATP-binding Cassette Transporter A1 by Protecting It from Thiol Protease-mediated Degradation

Arakawa

Yokoyama

2002

Journal of Biological Chemistry

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186

179

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ATP-binding cassette transporter (ABC) A1 was increased by apolipoprotein A-I without an increase of its message in THP-1 cells. The pulse label study demonstrated that apoA-I retarded degradation of ABCA1. Similar changes were demonstrated by apoA-II, but the effect of high density lipoprotein was almost negligible on the basis of equivalent protein concentration. Thiol protease inhibitors (leupeptin and N-acetyl-Leu-Leunorleucinal (ALLN)) increased ABCA1 and slowed its decay in the cells, whereas none of the proteosome-specific inhibitor lactacystin, other protease inhibitors, or the lysosomal inhibitor NH 4 Cl showed such effects. The effects of apoA-I and ALLN were additive for the increase of ABCA1, and the apoA-I-mediated cellular lipid release was enhanced by ALLN. The data suggest that ABCA1 is rapidly degraded by a thiol protease(s) in the cells unless helical apolipoproteins in their lipid-free form stabilize ABCA1 by protecting it from proteasemediated degradation.Helical apolipoproteins such as apoA-I, apoA-II, apoA-IV, and apoE interact with cell surfaces and generate high density lipoprotein (HDL) 1 by removing cellular phospholipid and cholesterol (1-3). The reaction is recognized as one of the major pathways of cellular cholesterol release along with the diffusion-mediated nonspecific cholesterol efflux (4). Fibroblasts from patients with a genetic defect of plasma HDL lack the interaction with apolipoprotein, indicating that this reaction is a main source of plasma HDL (5, 6). This view is supported by the finding that probucol, which markedly reduces plasma HDL, blocks the cell-apolipoprotein interaction (7-9). Mutations were identified in ATP-binding cassette transporter (ABC) A1 with many HDL-deficient families (10 -12), so that this protein is considered as a key for generation of HDL by the apolipoprotein-cell interaction and release of cellular cholesterol by this pathway.Regulation of ABCA1 expression is primarily by cellular cholesterol level through oxysterol as a ligand for the nuclear receptor liver X receptor (LXR) that acts in a heterodimer with retinoid X receptor (RXR) (13-15). The ligands for RXR (such as retinoids) in this receptor system also up-regulate the ABCA1 gene expression (14,15). In certain types of cell such as RAW264, cyclic AMP and its analogues markedly increase the ABCA1 message and protein by an unknown mechanism (16, 17). In THP-1 cells, differentiation by phorbol ester induces an increase in ABCA1 message level (18). ABCA1 was found in early and late endosomes so that the lysosomal pathway was suggested for its degradation (19). More recently, proteolytic degradation was indicated as a factor involved in regulation of the cellular level of ABCA1 (20). EXPERIMENTAL PROCEDURESCell Culture-THP-1 cells were maintained in RPMI 1640 (Iwaki) containing 10% fetal bovine serum (PAA laboratories) in a humidified atmosphere of 5% CO 2 and 95% air. Differentiation of THP-1 monocytes into macrophages was induced by culturing the cells at a density of 3.0 ϫ 106 cells/well ...

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Apolipoprotein-mediated cellular cholesterol/phospholipid efflux and plasma high density lipoprotein level in mice

Cited by 40 publications

References 51 publications

Probucol Inactivates ABCA1 in the Plasma Membrane with Respect to Its Mediation of Apolipoprotein Binding and High Density Lipoprotein Assembly and to Its Proteolytic Degradation

Probucol Inactivates ABCA1 in the Plasma Membrane with Respect to Its Mediation of Apolipoprotein Binding and High Density Lipoprotein Assembly and to Its Proteolytic Degradation

Apolipoprotein A-I Activates Protein Kinase Cα Signaling to Phosphorylate and Stabilize ATP Binding Cassette Transporter A1 for the High Density Lipoprotein Assembly

Helical Apolipoproteins Stabilize ATP-binding Cassette Transporter A1 by Protecting It from Thiol Protease-mediated Degradation

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