Variability of cholesterol accessibility in human red blood cells measured using a bacterial cholesterol-binding toxin
Year: 2017
Type: article
Study design: Observational Study
Abstract: Cholesterol partitions into accessible and sequestered pools in cell membranes. Here, we describe a new assay using fluorescently-tagged anthrolysin O, a cholesterol-binding bacterial toxin, to measure accessible cholesterol in human red blood cells (RBCs). Accessible cholesterol levels were stable within individuals, but varied >10 fold among individuals. Significant variation was observed among ethnic groups (Blacks>Hispanics>Whites). Variation in accessibility of RBC cholesterol was unrelated to the cholesterol content of RBCs or plasma, but was associated with the phospholipid composition of the RBC membranes and with plasma triglyceride levels. Pronase treatment of RBCs only modestly altered cholesterol accessibility. Individuals on hemodialysis, who have an unexplained increase in atherosclerotic risk, had significantly higher RBC cholesterol accessibility. Our data indicate that RBC accessible cholesterol is a stable phenotype with significant inter-individual variability. Factors both intrinsic and extrinsic to the RBC contribute to variation in its accessibility. This assay provides a new tool to assess cholesterol homeostasis among tissues in humans.
Source: eLife
DOI: 10.7554/elife.23355
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: National Science Foundation, Howard Hughes Medical Institute, Welch Foundation, American Heart Association, Kansas IDeA Network of Biomedical Research Excellence, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Center for Research Resources, National Center for Advancing Translational Sciences, Office of Experimental Program to Stimulate Competitive Research
Awards: G1327449000, UT Southwestern Center for Translational Medicine (UL1/KL2/TL1), G1755609097, G2190490477, Molecular Basis of Cholesterol Metabolism, G3330230796, G3395997892, G3413102474, MRI: Acquisition of a high-sensitivity triple quadrupole mass spectrometer for the Kansas Lipidomics Research Center, G363963801, Collaborative Research: Metabolomic Profiling and Functions of Oxidized Membrane Lipids in Plant Stress Responses, G4670072506, G527540128, Metabolomic Profiling of Lipids and Their Compositional Dynamics in Plant Stress Responses, G7286552280, G7320545758, G750898885, G8091850500, Phase IV: Improvement of the Academic Research Infrastructure, Acquisition of Mass Spectrometers for the Kansas State University Functional Genomics Laboratories, G9000031876, G9000037139, G9000063737, G9000067976, G9000075811, G9000246230, G9349655
OpenAlex ID: W2586630646