Selenoprotein K is required for palmitoylation of CD36 in macrophages: implications in foam cell formation and atherogenesis (P1102)

Abstract

Abstract Selenoprotein K (Selk) is an endoplasmic reticulum transmembrane protein important for calcium flux and macrophage activation, but its role in foam cell formation and atherosclerosis has not been evaluated. Bone marrow-derived macrophages (BMDM) from Selk-/- mice exhibited decreased uptake of modified low density lipoprotein and foam cell formation compared to wild-type controls, and the differences were eliminated with anti-CD36 blocking antibody. CD36 expression was decreased in TNFα-stimulated Selk-/- BMDM compared to wild-type controls. Fluorescence microscopy revealed TNFα-induced clustering of CD36 in wild-type BMDM indicative of lipid raft localization, which was absent in Selk-/- BMDM. Immunoprecipitation showed Selk-/- BMDM have decreased CD36 palmitoylation, which is crucial for both stabilizing CD36 expression and directing its localization to lipid rafts. To assess if this phenomenon had a role in atherogenesis, high-fat diet was fed to irradiated Ldlr-/- mice reconstituted with bone marrow from Selk-/- or wild-type mice. Selk was detected in aortic plaques of controls, particularly in macrophages. Selk deficiency in immune cells led to reduction in atherosclerotic lesion formation without affecting leukocyte migration into the arterial wall. These findings suggest that Selk is important for stable, localized expression of CD36 in macrophages during inflammation, thereby contributing to foam cell formation and atherogenesis.