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Cholesterol crystal nucleation from enzymatically modified low-density lipoproteins: combined effect of sphingomyelinase and cholesterol esterase
Journal article   Peer reviewed

Cholesterol crystal nucleation from enzymatically modified low-density lipoproteins: combined effect of sphingomyelinase and cholesterol esterase

Andrew J Guarino, Thomas N Tulenko and Steven P Wrenn
Biochemistry (Easton), v 43(6), pp 1685-1693
17 Feb 2004
PMID: 14769046

Abstract

Lipoproteins, LDL - chemistry Sphingomyelin Phosphodiesterase - chemistry Ergosterol - chemistry Humans Crystallization Spectrometry, Fluorescence Phosphatidylcholines - chemistry Type C Phospholipases - chemistry Ergosterol - analogs & derivatives Cholesterol - chemistry Drug Synergism Fluorescence Resonance Energy Transfer Dansyl Compounds - chemistry Liposomes Sterol Esterase - chemistry Microscopy, Fluorescence
An assay detecting and quantifying cholesterol nucleation from low-density lipoproteins has been established. Förster resonance energy transfer between dehydroergosterol and dansylated lecithin becomes significantly alleviated as a consequence of conucleation of dehydroergosterol and cholesterol. The assay, in combination with dynamic light scattering, absorbance spectroscopy, and fluorescence microscopy, can be used to study aggregation and nucleation in model blood systems. Human plasma LDL was labeled with dehydroergosterol and dansylated lecithin by incubation with donor multilamellar liposomes and isolated by centrifugation. Exposure of labeled LDL (0.5 mg/mL of total lipids) to sphingomyelinase (0.0-0.2 unit/mL) led to modest particle aggregation but produced no changes in energy transfer and no crystallization. However, addition of sphingomyelinase produced significant particle aggregation, nucleation, and crystallization, in a dose-dependent fashion, in samples that were previously treated with the enzyme, cholesterol esterase (0.2 unit/mL). The combination of cholesterol esterase and sphingomyelinase led to a significant alleviation of energy transfer, which preceded by 24 h the appearance of fluorescent, microscopic sterol crystals. These results point to a synergistic effect between cholesterol esterase and sphingomyelinase, suggesting that mere aggregation of LDL is insufficient to promote nucleation, and crystal formation likely proceeds in the intracellular space after LDL uptake by macrophages.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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