Variability of cholesterol accessibility in human red blood cells measured using a bacterial cholesterol-binding toxin
- Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, United States
- University of Texas Southwestern Medical Center, United States
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.
Article and author information
Author details
Arun Radhakrishnan
Funding
Howard Hughes Medical Institute
- Rima S Chakrabarti
- Sally A Ingham
- Helen H Hobbs
National Institutes of Health (PO1 HL20948)
- Austin Gay
- Jonathan C Cohen
- Arun Radhakrishnan
- Helen H Hobbs
Welch Foundation (I-1793)
- Arun Radhakrishnan
American Heart Association (12SDG12040267)
- Arun Radhakrishnan
National Institutes of Health (5T32-GM008203)
- Austin Gay
National Institutes of Health (UL1TR001105)
- Julia Kozlitina
- Helen H Hobbs
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: All study protocols were approved by the Institutional Review Board (IRB) of the University of Texas Southwestern Medical Center, and all subjects provided written informed consent. Each participant completed a detailed staff-administered survey, including questions about socioeconomic status, medical history and medication use. Ancestry was self-reported.
Copyright
© 2017, Chakrabarti et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Variability of cholesterol accessibility in human red blood cells measured using a bacterial cholesterol-binding toxin
eLife 6:e23355.
https://doi.org/10.7554/eLife.23355
