Artículo
Nitro-oleic acid, a ligand of CD36, reduces cholesterol accumulation by modulating oxidized-LDL uptake and cholesterol efflux in RAW264.7 macrophages
Vazquez, Matias Maximiliano
; Gutierrez, Maria Victoria; Salvatore, Sonia Rosana; Puiatti, Marcelo
; Actis Dato, Virginia
; Chiabrando, Gustavo Alberto
; Freeman, Bruce A.; Schopfer, Francisco Jose; Bonacci, Gustavo Roberto
Fecha de publicación:
06/2020
Editorial:
Elsevier B.V.
Revista:
Redox Biology
ISSN:
2213-2317
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Macrophages play a pivotal role in the early stages of atherosclerosis development; they excessively accumulate cholesterol in the cytosol in response to modified Low Density Lipoprotein (mLDL). The mLDL are incorporated through scavenger receptors. CD36 is a highaffinity cell surface scavenger receptor that facilitates the binding and uptake of long-chain fatty acids and mLDL into the cell. Numerous structurally diverse ligands can initiate signaling responses through CD36 to regulate cell metabolism, migration, and angiogenesis. Nitro-fatty acids are endogenous electrophilic lipid mediators that react with and modulate the function ofmultiple enzymes and transcriptional regulatory proteins. These actions induce the expression of several anti-inflammatory and cytoprotective genes and limit pathologic responses in experimental models of atherosclerosis, cardiac ischemia/reperfusion, and inflammatory diseases. Pharmacological and genetic approaches were used to explore the actions of nitro-oleic acid(NO2-OA) on macrophage lipid metabolism. NO2-OA dose-dependently increased CD36 expression in RAW264.7 macrophages and this up-regulation was abrogated in BMDM from Nrf2-KO mice. Ligand binding analysis revealed that NO2-OA specifically interacts with CD36 limiting the binding and uptake of mLDL. Docking analysis shows that NO2-OA establishes a low binding energy interaction with the alpha helix containing Lys164 in CD36. NO2-OA alsorestored autophagy flux in mLDL-loaded macrophages, thus reversing cholesterol deposition within the cell. In aggregate, these results indicate that NO2-OA reduces cholesterol uptake by binding to CD36 and increases cholesterol efflux by restoring autophagy.
Palabras clave:
ATHEROSCLEROSIS
,
CD36
,
MACROPHAGES
,
NITRO-OLEIC ACID
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Identificadores
Colecciones
Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos(INFIQC)
Articulos de INST.DE INVESTIGACIONES EN FISICO- QUIMICA DE CORDOBA
Articulos de INST.DE INVESTIGACIONES EN FISICO- QUIMICA DE CORDOBA
Citación
Vazquez, Matias Maximiliano; Gutierrez, Maria Victoria; Salvatore, Sonia Rosana; Puiatti, Marcelo; Actis Dato, Virginia; et al.; Nitro-oleic acid, a ligand of CD36, reduces cholesterol accumulation by modulating oxidized-LDL uptake and cholesterol efflux in RAW264.7 macrophages; Elsevier B.V.; Redox Biology; 36; 6-2020; 1-49
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