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Tytuł:
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Fisetin, via CKIP-1/REGγ, limits oxidized LDL-induced lipid accumulation and senescence in RAW264.7 macrophage-derived foam cells.
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Autorzy:
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Jia Q; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200031, China.
Cao H; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200031, China.
Shen D; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200031, China. Electronic address: .
Yan L; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200031, China.
Chen C; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200031, China.
Xing S; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200031, China.
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Źródło:
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European journal of pharmacology [Eur J Pharmacol] 2019 Dec 15; Vol. 865, pp. 172748. Date of Electronic Publication: 2019 Oct 23.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: 2005- : Amsterdam : Elsevier Science
Original Publication: Amsterdam, North Holland Pub. Co.
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MeSH Terms:
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Autoantigens/*metabolism
Carrier Proteins/*metabolism
Flavonoids/*pharmacology
Foam Cells/*drug effects
Lipoproteins, LDL/*metabolism
Proteasome Endopeptidase Complex/*metabolism
Animals ; Cellular Senescence/drug effects ; Flavonols ; Foam Cells/metabolism ; Lipid Metabolism/drug effects ; Mice ; RAW 264.7 Cells ; Signal Transduction/drug effects
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Contributed Indexing:
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Keywords: CKIP-1/REGγ signaling; Fisetin; Lipid accumulation; RAW264.7; Senescence
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Substance Nomenclature:
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0 (Autoantigens)
0 (CKIP-1 protein, mouse)
0 (Carrier Proteins)
0 (Flavonoids)
0 (Flavonols)
0 (Ki antigen)
0 (Lipoproteins, LDL)
0 (oxidized low density lipoprotein)
EC 3.4.25.1 (Proteasome Endopeptidase Complex)
OO2ABO9578 (fisetin)
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Entry Date(s):
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Date Created: 20191027 Date Completed: 20200520 Latest Revision: 20211204
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Update Code:
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20240104
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DOI:
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10.1016/j.ejphar.2019.172748
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PMID:
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31655030
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To test the hypothesis that the flavonoid compound, fisetin, protects macrophages from lipid accumulation and senescence through regulation of casein kinase 2-interacting protein-1 (CKIP-1)/REGγ (11S regulatory particles, 28 kDa proteasome activator, proteasome activator subunit 3) signaling. RAW264.7 macrophage cells were exposed to 100 μg/ml oxidized low-density lipoprotein (ox-LDL) with or without 20 μg/ml fisetin for 24 h. Cell viability was detected by CCK-8 after 1 h. Intracellular lipid accumulation was measured using Oil Red O staining. Total cholesterol (TC) and free cholesterol (FC) contents were measured using assay kits, and cell senescence was inferred by β-gal staining. Protein expression levels of CKIP-1, REGγ, organic cation transporter 1 (Oct-1), lectin-like oxidized LDL receptor-1 (LOX-1), tumor suppressor protein p53 (p53), cell cycle regulatory protein p21 (p21), and multiple tumor suppressor-1 (p16) were detected by immunofluorescence and confirmed by Western blot. Stimulating RAW264.7 macrophage cells with 100 μg/ml ox-LDL for 24 h induced the formation of foam cells, increased intracellular lipid accumulation, increased TC and FC content, and promoted cell senescence. Furthermore, cells induced with 100 μg/ml ox-LDL for 24 h showed decreased CKIP-1 and REGγ protein, while the expressions of Oct-1, LOX-1, p53, p21 and p16 were increased. In contrast, treatment with 20 μg/ml fisetin reversed 100 μg/ml ox-LDL effects to increase cell viability, and decrease β-gal staining, intracellular lipid levels and TC and FC levels. These beneficial effects were associated with increased CKIP-1 and REGγ and decreased Oct-1, LOX-1, p53, p21, and p16 protein expression. Results indicated that fisetin limited ox-LDL-mediated lipid accumulation and senescence in RAW264.7 macrophage-derived foam cells. The mechanism underlying these effects may involve regulation of CKIP-1/REGγ signaling.
(Copyright © 2019 Elsevier B.V. All rights reserved.)