tailieunhanh - Báo cáo khoa học: Protection of chylomicron remnants from oxidation by incorporation of probucol into the particles enhances their uptake by human macrophages and increases lipid accumulation in the cells

The effects of protection of chylomicron remnants from oxidation on their uptake and induction of lipid accumula-tion in macrophages were investigated using chylomicron remnant-like particles (CRLPs) containing the lipophilic antioxidant drug, probucol, andmacrophages derived from thehumanmonocyte cell line, total lipidcontent of THP-1 macrophages was markedly higher (·) after 48 h of incubation of THP-1 macrophages with CRLPs containing probucol (pCRLPs) when compared to CRLPs without probucol, and this was because of increases in tri-acylglycerol (·) and cholesterol (·) levels, while cho-lesteryl ester concentrations were not significantly changed | Eur. J. Biochem. 271 2417-2427 2004 FEBS 2004 doi Protection of chylomicron remnants from oxidation by incorporation of probucol into the particles enhances their uptake by human macrophages and increases lipid accumulation in the cells Elizabeth H. Moore1 Mariarosaria Napolitano2 Michael Avella1 Fatos Bejta1 Keith E. Suckling3 Elena Bravo2 and Kathleen M. Botham1 1 Department of Veterinary Basic Sciences The Royal Veterinary College London UK 2Istituto Superiore di Sanita Department of Hematology Oncology and Molecular Medicine Viale Regina Elena Rome Italy Glaxo SmithKline Medicines Research Centre Stevenage Herts. UK The effects of protection of chylomicron remnants from oxidation on their uptake and induction of lipid accumulation in macrophages were investigated using chylomicron remnant-like particles CRLPs containing the lipophilic antioxidant drug probucol and macrophages derived from the human monocyte cell line THP-1. The total lipid content of THP-1 macrophages was markedly higher after 48 h of incubation of THP-1 macrophages with CRLPs containing probucol pCRLPs when compared to CRLPs without probucol and this was because of increases in triacylglycerol and cholesterol levels while cholesteryl ester concentrations were not significantly changed. Determination of the uptake of CRLPs and pCRLPs by the cells using particles labelled with the fluorescent probe 1 1 -dioctadecyl-3 3 3 3 -tetramethylindo-carbocyanine perchlorate showed that pCRLPs are taken up at a faster rate than CRLPs. The synthesis of triacylglycerol as measured by the incorporation of 3H oleate and 3H glycerol was also increased in macrophages incubated with pCRLPs as compared to CRLPs without probucol but phospholipid and cholesteryl ester formation from 3H oleate was unaffected. In addition no differences between the effects of CRLPs and pCRLPs on the expression of mRNA for a range of genes believed to be involved in lipoprotein uptake .