Effects of cholesterol in chylomicron remnant models of lipid emulsions on apoE-mediated uptake and cytotoxicity of macrophages
Autor: | Kyoko Wakita, Shin-ya Morita, Tetsurou Handa, Minoru Nakano, Atsushi Sakurai, Yuko Deharu |
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Jazyk: | angličtina |
Rok vydání: | 2005 |
Předmět: |
Apolipoprotein E
Cell Survival Surface Properties Chylomicron Remnants Phospholipid Apoptosis QD415-436 Biochemistry Cell Line phosphatidylcholine head group separation Mice chemistry.chemical_compound Apolipoproteins E Endocrinology Chylomicron remnant Chylomicrons polycyclic compounds Animals Humans apolipoprotein E Cholesterol Macrophages digestive oral and skin physiology Cell Biology J774 macrophages chemistry Low-density lipoprotein Emulsion Emulsions lipids (amino acids peptides and proteins) Heparan Sulfate Proteoglycans Low Density Lipoprotein Receptor-Related Protein-1 Lipoprotein Chylomicron |
Zdroj: | Journal of Lipid Research, Vol 46, Iss 10, Pp 2214-2220 (2005) |
ISSN: | 0022-2275 |
Popis: | Chylomicron remnants have been suggested to be involved in the development of atherosclerosis. To investigate the mechanisms of chylomicron remnant-induced atherosclerosis, we prepared cholesterol (Chol)-containing emulsion particles as models for chylomicron remnants. Chol markedly increased the apolipoprotein E (apoE) binding maximum of emulsions without changing the binding affinity and thereby promoted emulsion uptake by J774 macrophages. Fluorescence measurements showed that Chol increased acyl chain order and head group hydration of the surface phospholipid (PL) layer of emulsions. The binding maximum of apoE was closely correlated with the hydration and the increase in the PL head group separation at the emulsion surface. From experiments using inhibitors for lipoprotein receptors, heparan sulfate proteoglycans and low density lipoprotein receptor-related protein were found to be the major contributors to the uptake of Chol-containing emulsions. Trypan blue dye exclusion revealed that the uptake of Chol-containing emulsions induced cytotoxicity to J774 macrophages. This study proposes a mechanism of atherosclerosis induced by chylomicron remnants. |
Databáze: | OpenAIRE |
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