RESUMO
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 high-affinity 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 of multiple 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. Pure synthetic 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, thus 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 also restored 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.
Assuntos
Antígenos CD36 , Ácido Oleico , Animais , Antígenos CD36/genética , Colesterol , Células Espumosas/metabolismo , Ligantes , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , CamundongosRESUMO
La mayoria de las propiedades fisicoquímicas y sensoriales de los extruidos depende de la extensión de la degradación del lmidón. Un extruido de cereal tiene propiedades fisicoquímicas similares a una mezcla de almidón crudo, gelatinizado y dextrinizado. En base a esto postulado, se elaboraron modelos de mezclas cereal: oleaginosa, y se aplicaron diferentes técnicas analíticas para su caracterización. Los resultados revelaron que la muestra extruida de maíz: soja (70:30) en estudio, se asemejaba a una mezcla maíz: soja moderadamente dextrinizada obtenida en el laboratorio. Por consiguiente, podría ser usada en la preparación de papillas o alimentos precocidos