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Molecular signaling operated by a diet‐compatible mixture of oxysterols in up‐regulating CD36 receptor in CD68 positive cells
Author(s) -
Leonarduzzi Gabriella,
Gargiulo Simona,
Gamba Paola,
Perrelli MariaGiulia,
Castellano Isabella,
Sapino Anna,
Sottero Barbara,
Poli Giuseppe
Publication year - 2010
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200900493
Subject(s) - oxysterol , cd36 , scavenger receptor , microbiology and biotechnology , receptor , signal transduction , biology , chemistry , foam cell , macrophage , biochemistry , cholesterol , lipoprotein , in vitro
Oxidation of dietary cholesterol during food storage and processing, and/or that of endogenous cholesterol in the presence of increased steady‐state levels of reactive oxygen species, leads to the production of derivatives, termed oxysterols. Among the biochemical effects exerted by an oxysterol mixture, it has recently been observed that marked up‐regulation of CD36 scavenger receptor on macrophage cells plays a primary role in foam cell formation. This article reports evidence of a significant co‐localization of CD36 receptor with cells of the macrophage lineage, i.e. CD68 positive cells, LDL apoprotein B100 and lipids in human advanced atherosclerotic lesions. In addition, it provides a comprehensive analysis of the molecular signaling operated by a nutritionally relevant mixture of oxysterols in overexpressing CD36 receptor in cells of the macrophage lineage. The involvement of a G protein, Src, phospholipase C cascade and peroxisome proliferator‐activated receptor γ in oxysterol‐mediated signaling was demonstrated by using selective inhibitors, while the central role of the downstream protein kinase Cδ and extracellular signal‐regulated kinase pathways in oxysterol‐induced enhancement of CD36 was conclusively proved by means of small interfering RNA (siRNA) technology.