The lipid moiety 7-ketocholesteryl-9-carboxynonanoate mediates binding interaction of oxLDL to LOX-1 and upregulates ABCA1 expression through PPARγ

Li, Jingda; Xiu, Zhilong; Wang, Renjun; Yu, Chengjie; Chi, Yan; Qin, Jian‐Zhong; Fu, Changzhen; Matsuura, Eiji; Liu, Qingping

doi:10.1016/j.lfs.2017.03.024

Cited by 9 publications

(10 citation statements)

References 35 publications

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“…As shown in Table , the S. chamaejasme extract with 10 U/mL LOX had the best binding affinity. The binding of a ligand to LOX was quantified using the enhancement factor (%) = (A 1 /A 2 ) × 100, where A 1 and A 2 are the amount of the compound bound to LOX and total amount of the compound in the reaction, respectively . The results revealed that compound 2 in the S. chamaejasme extract exhibited the highest binding affinity (44.84%), followed by compounds 1 (43.87%), 3 (29.36%), 4 (28.76%), and 5 (19.24%).…”

Section: Resultsmentioning

confidence: 99%

Development of a method to screen and isolate bioactive constituents from Stellera chamaejasme by ultrafiltration and liquid chromatography combined with semi‐preparative high‐performance liquid chromatography and high‐speed counter current chromatography

Hou

Xia

Liu

et al. 2019

J of Separation Science

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A simple and efficient method based on ultrafiltration with liquid chromatography and mass spectrometry was used for the rapid screening and identification of ligands in the extracts of Stellera chamaejasme. The bound ligands, i.e. daphnoretin, isopimpinellin, chamaechromone, neochamaejasmin A, and chamaejasmine (purity of 96.8, 90.75, 91.41, 93.98, and 98.91%, respectively), were separated by semi‐preparative high‐performance liquid chromatography combined with high‐speed counter‐current chromatography. To the best of our knowledge, this is the first study to report the detection of potent lipoxidase and lactate dehydrogenase inhibitors in Stellera chamaejasme extracts. The results demonstrate that our method of ultrafiltration with liquid chromatography and mass spectrometry combined with mixed chromatography can be used to screen and confirm the bioactivity of all isolated compounds. This method also eliminates the need for separation of inactive compounds, thereby improving efficiency when studying bioactive substances. For some complex mixtures, neither semi‐preparative high‐performance liquid chromatography nor high‐speed counter‐current chromatography can purify all the target active compounds with high purity in a one‐step separation. The combination of the two methods allow for efficient purification of target bioactive compounds with different polarities and physicochemical properties based on their complementary properties.

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Section: Resultsmentioning

confidence: 99%

Development of a method to screen and isolate bioactive constituents from Stellera chamaejasme by ultrafiltration and liquid chromatography combined with semi‐preparative high‐performance liquid chromatography and high‐speed counter current chromatography

Hou

Xia

Liu

et al. 2019

J of Separation Science

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“…Emerging evidence indicated that LOX-1 could be negatively regulated by PPAR- γ activation in the treatment of atherosclerosis with TZDs [9, 22]. LOX-1 mediated suppression of ABCA1 in macrophages could be reversed by TZDs, which improved the reverse cholesterol transport and prevented the foam cell formation and ox-LDL accumulation on the arterial wall in the development of atherosclerosis [23, 24]. However, the precise role of PPAR- γ in ox-LDL-induced endothelial cells remained unclear.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor-γ Antagonizes LOX-1-Mediated Endothelial Injury by Transcriptional Activation of miR-590-5p

Zhao

Zhu

et al. 2019

PPAR Research

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Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is one of the major receptors expressed on the endothelium of arterial wall with a key role in endothelial dysfunction and the development of atherosclerosis. Recent evidence suggested that LOX-1 is upregulated under the condition of insulin resistance and could be suppressed by the antidiabetic drugs. We previously also confirmed that Thiazolidinedione (TZD) has the inhibitory effect on LOX-1 in ox-LDL-induced endothelial cells. However, the underlying mechanism is unclear. Here we showed that Rosiglitazone treatment significantly attenuated the expressions of LOX-1, ICAM-1, VCAM-1, p47phox, and the atherosclerotic lesions in ApoE-/- mice with high-fat diet. In vitro, we revealed that Rosiglitazone inhibited LOX-1 by regulating miR-590-5p. Ox-LDL-mediated ICAM-1, VCAM-1, and p47phox were significantly reduced by Rosiglitazone, but all reversed after pretreating the cells with antagomiR-590-5p. Induction with Rosiglitazone activated PPAR-γ and promoted its nuclear translocation in cultured human umbilical vein endothelial cells (HUVECs). The nuclear PPAR-γ upregulated the miR-590-5p level through binding to its transcriptional promoter region. Retaining PPAR-γ in cytoplasm by transfecting with PPAR-γ⊿NLS plasmid in HUVECs failed to activate miR-590-5p. Mutation of the promoter region of PPAR-γ also reduced the miR-590-5p promoter luciferase activity. Collectively, these data indicated that PPAR-γ may have the therapeutic potential in atherosclerosis via the transcriptional regulation of miR-590-5p in endothelial cells.

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“…This is an important function as 7-KC, 7α and 7β-hydroxycholesterol, products of non-enzymatic cholesterol oxidation, together with 27-hydroxycholesterol (produced via cholesterol 27-hydroxilase, CYP27A1), are the major oxysterols found in atherosclerotic lesions [ 72 ]. On this note, the ω-carboxyl group in 7-KC-9-carboxynonanoate (oxLig-1) is an epitope of oxLDL that mediates the binding of oxLDL to LOX-1, leading to the upregulation of ABCA1 through PPARγ-LXRα-ABCA1 signaling pathway [ 87 ]. Moreover, the binding of oxLDL to CD36 after oxLig-1 stimulation, upregulates caveolin-1 and promote cholesterol efflux in macrophages, in a process mediated by Src-JNK/ERK1/2-NF-κB signal transduction [ 87 ].…”

Section: Reverse Cholesterol Transportmentioning

confidence: 99%

“…On this note, the ω-carboxyl group in 7-KC-9-carboxynonanoate (oxLig-1) is an epitope of oxLDL that mediates the binding of oxLDL to LOX-1, leading to the upregulation of ABCA1 through PPARγ-LXRα-ABCA1 signaling pathway [ 87 ]. Moreover, the binding of oxLDL to CD36 after oxLig-1 stimulation, upregulates caveolin-1 and promote cholesterol efflux in macrophages, in a process mediated by Src-JNK/ERK1/2-NF-κB signal transduction [ 87 ]. Caveolin-1 is the main structural protein of caveolae and is involved in intracellular cholesterol trafficking and removal [ 88 ].…”

Section: Reverse Cholesterol Transportmentioning

confidence: 99%

Molecular Pathways Underlying Cholesterol Homeostasis

et al. 2018

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Cholesterol is an essential molecule that exerts pleiotropic actions. Although its presence is vital to the cell, its excess can be harmful and, therefore, sustaining cholesterol homeostasis is crucial to maintaining proper cellular functioning. It is well documented that high plasma cholesterol concentration increases the risk of atherosclerotic heart disease. In the last decades, several studies have investigated the association of plasma cholesterol concentrations and the risk of cardiovascular diseases as well as the signaling pathways involved in cholesterol homeostasis. Here, we present an overview of several mechanisms involved in intestinal cholesterol absorption, the regulation of cholesterol synthesis and uptake. We also discuss the importance of reverse cholesterol transport and transintestinal cholesterol transport to maintain cholesterol homeostasis and prevent atherosclerosis development. Additionally, we discuss the influence of dietary cholesterol on plasma cholesterol concentration and the new recommendations for cholesterol intake in a context of a healthy dietary pattern.

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The lipid moiety 7-ketocholesteryl-9-carboxynonanoate mediates binding interaction of oxLDL to LOX-1 and upregulates ABCA1 expression through PPARγ

Cited by 9 publications

References 35 publications

Development of a method to screen and isolate bioactive constituents from Stellera chamaejasme by ultrafiltration and liquid chromatography combined with semi‐preparative high‐performance liquid chromatography and high‐speed counter current chromatography

Development of a method to screen and isolate bioactive constituents from Stellera chamaejasme by ultrafiltration and liquid chromatography combined with semi‐preparative high‐performance liquid chromatography and high‐speed counter current chromatography

Peroxisome Proliferator-Activated Receptor-γ Antagonizes LOX-1-Mediated Endothelial Injury by Transcriptional Activation of miR-590-5p

Molecular Pathways Underlying Cholesterol Homeostasis

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