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Aspirin Interacts with Cholesterol-Containing Membranes in a pH-Dependent Manner

[Image: see text] Aspirin has been used for broad therapeutic treatment, including secondary prevention of cardiovascular disease associated with increased cholesterol levels. Aspirin and other nonsteroidal anti-inflammatory drugs have been shown to interact with lipid membranes and change their bio...

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Autores principales: Krmic, Michael, Perez, Escarlin, Scollan, Patrick, Ivanchenko, Katherine, Gamez Hernandez, Alondra, Giancaspro, Joseph, Rosario, Juan, Ceja-Vega, Jasmin, Gudyka, Jamie, Porteus, Riley, Lee, Sunghee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666536/
https://www.ncbi.nlm.nih.gov/pubmed/37939382
http://dx.doi.org/10.1021/acs.langmuir.3c02242
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author Krmic, Michael
Perez, Escarlin
Scollan, Patrick
Ivanchenko, Katherine
Gamez Hernandez, Alondra
Giancaspro, Joseph
Rosario, Juan
Ceja-Vega, Jasmin
Gudyka, Jamie
Porteus, Riley
Lee, Sunghee
author_facet Krmic, Michael
Perez, Escarlin
Scollan, Patrick
Ivanchenko, Katherine
Gamez Hernandez, Alondra
Giancaspro, Joseph
Rosario, Juan
Ceja-Vega, Jasmin
Gudyka, Jamie
Porteus, Riley
Lee, Sunghee
author_sort Krmic, Michael
collection PubMed
description [Image: see text] Aspirin has been used for broad therapeutic treatment, including secondary prevention of cardiovascular disease associated with increased cholesterol levels. Aspirin and other nonsteroidal anti-inflammatory drugs have been shown to interact with lipid membranes and change their biophysical properties. In this study, mixed lipid model bilayers made from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) or 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) comprising varying concentrations of cholesterol (10:1, 4:1, and 1:1 mole ratio of lipid:chol), prepared by the droplet interface bilayer method, were used to examine the effects of aspirin at various pH on transbilayer water permeability. The presence of aspirin increases the water permeability of POPC bilayers in a concentration-dependent manner, with a greater magnitude of increase at pH 3 compared to pH 7. In the presence of cholesterol, aspirin is similarly shown to increase water permeability; however, the extent of the increase depends on both the concentration of cholesterol and the pH, with the least pronounced enhancement in water permeability at high cholesterol levels at pH 7. A fusion of data from differential scanning calorimetry, confocal Raman microspectrophotometry, and interfacial tensiometric measurements demonstrates that aspirin can promote significant thermal, structural, and interfacial property perturbations in the mixed-lipid POPC or DOPC membranes containing cholesterol, indicating a disordering effect on the lipid membranes. Our findings suggest that aspirin fluidizes phosphocholine membranes in both cholesterol-free and cholesterol-enriched states and that the overall effect is greater when aspirin is in a neutral state. These results confer a deeper comprehension of the divergent effects of aspirin on biological membranes having heterogeneous compositions, under varying physiological pH and different cholesterol compositions, with implications for a better understanding of the gastrointestinal toxicity induced by the long term use of this important nonsteroidal anti-inflammatory molecule.
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spelling pubmed-106665362023-11-23 Aspirin Interacts with Cholesterol-Containing Membranes in a pH-Dependent Manner Krmic, Michael Perez, Escarlin Scollan, Patrick Ivanchenko, Katherine Gamez Hernandez, Alondra Giancaspro, Joseph Rosario, Juan Ceja-Vega, Jasmin Gudyka, Jamie Porteus, Riley Lee, Sunghee Langmuir [Image: see text] Aspirin has been used for broad therapeutic treatment, including secondary prevention of cardiovascular disease associated with increased cholesterol levels. Aspirin and other nonsteroidal anti-inflammatory drugs have been shown to interact with lipid membranes and change their biophysical properties. In this study, mixed lipid model bilayers made from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) or 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) comprising varying concentrations of cholesterol (10:1, 4:1, and 1:1 mole ratio of lipid:chol), prepared by the droplet interface bilayer method, were used to examine the effects of aspirin at various pH on transbilayer water permeability. The presence of aspirin increases the water permeability of POPC bilayers in a concentration-dependent manner, with a greater magnitude of increase at pH 3 compared to pH 7. In the presence of cholesterol, aspirin is similarly shown to increase water permeability; however, the extent of the increase depends on both the concentration of cholesterol and the pH, with the least pronounced enhancement in water permeability at high cholesterol levels at pH 7. A fusion of data from differential scanning calorimetry, confocal Raman microspectrophotometry, and interfacial tensiometric measurements demonstrates that aspirin can promote significant thermal, structural, and interfacial property perturbations in the mixed-lipid POPC or DOPC membranes containing cholesterol, indicating a disordering effect on the lipid membranes. Our findings suggest that aspirin fluidizes phosphocholine membranes in both cholesterol-free and cholesterol-enriched states and that the overall effect is greater when aspirin is in a neutral state. These results confer a deeper comprehension of the divergent effects of aspirin on biological membranes having heterogeneous compositions, under varying physiological pH and different cholesterol compositions, with implications for a better understanding of the gastrointestinal toxicity induced by the long term use of this important nonsteroidal anti-inflammatory molecule. American Chemical Society 2023-11-08 /pmc/articles/PMC10666536/ /pubmed/37939382 http://dx.doi.org/10.1021/acs.langmuir.3c02242 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Krmic, Michael
Perez, Escarlin
Scollan, Patrick
Ivanchenko, Katherine
Gamez Hernandez, Alondra
Giancaspro, Joseph
Rosario, Juan
Ceja-Vega, Jasmin
Gudyka, Jamie
Porteus, Riley
Lee, Sunghee
Aspirin Interacts with Cholesterol-Containing Membranes in a pH-Dependent Manner
title Aspirin Interacts with Cholesterol-Containing Membranes in a pH-Dependent Manner
title_full Aspirin Interacts with Cholesterol-Containing Membranes in a pH-Dependent Manner
title_fullStr Aspirin Interacts with Cholesterol-Containing Membranes in a pH-Dependent Manner
title_full_unstemmed Aspirin Interacts with Cholesterol-Containing Membranes in a pH-Dependent Manner
title_short Aspirin Interacts with Cholesterol-Containing Membranes in a pH-Dependent Manner
title_sort aspirin interacts with cholesterol-containing membranes in a ph-dependent manner
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666536/
https://www.ncbi.nlm.nih.gov/pubmed/37939382
http://dx.doi.org/10.1021/acs.langmuir.3c02242
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