Journal article
Effect of sphingomyelinase-mediated generation of ceramide on aggregation of low-density lipoprotein
Langmuir, v 24(17), pp 9642-9647
02 Sep 2008
PMID: 18671414
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
This study addresses the response-to-retention hypothesis, which states that the subendothelial retention of atherogenic lipoproteins is the necessary and sufficient condition for the initiation of atherosclerosis. Here we focus on the relationship between the generation of ceramide in the low-density lipoprotein (LDL) phospholipid monolayer and the resulting aggregation of LDL particles. This study provides the first measurement of neutral, Mg (2+)-dependent Sphingomyelinase (Smase)-mediated ceramide formation from LDL-sphingomyelin and does so for a range of enzyme concentrations (0-0.22 units Smase/mL). The kinetics of ceramide generation was measured using a fluorescence assay for the above enzyme concentrations with a fixed substrate concentration (0.33 mg LDL/mL). The kinetics of LDL aggregate formation was measured by dynamic light scattering (DLS, method of cumulants) for identical enzyme concentrations. Ceramide concentration profiles were fit with a modification of the Michaelis-Menten model ( k a = 1.11 x 10 (-1) microM (-1) min (-1), k -a = 6.54 x 10 (2) microM (-1) min (-1), k 1 = 3.33 x 10 (1) microM (-1) min (-1), k -1 = 1.41 x 10 (-2) min (-1), k cat = 8.05 x 10 (1) min (-1), K M = 2.418 microM, k deact = 4.66 x 10 (-2) microM (-1) min (-1)) that accounts for the effects of enzyme attachment to the LDL monolayer and for deactivation of Smase due to product inhibition. LDL aggregation is described by a mass action model as explained in previous studies. A key result of this work is the finding that LDL aggregate size depends directly on ceramide concentration and is independent of enzyme concentration. This study demonstrates how principles of colloid science are relevant to important biomedical problems.
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Details
- Title
- Effect of sphingomyelinase-mediated generation of ceramide on aggregation of low-density lipoprotein
- Creators
- Michael J Walters - Department of Chemical and Biological Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, Pennsylvania 19104, USASteven P Wrenn
- Publication Details
- Langmuir, v 24(17), pp 9642-9647
- Publisher
- American Chemical Society; Washington, DC
- Grant note
- 5 R01GM071355 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemical and Biological Engineering
- Web of Science ID
- WOS:000258722100068
- Scopus ID
- 2-s2.0-51449106611
- Other Identifier
- 991014877668204721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Chemistry, Multidisciplinary
- Chemistry, Physical
- Materials Science, Multidisciplinary