Cholesterol under oxidative stress - How lipid membranes sense oxidation as cholesterol is being replaced by oxysterols

Waldemar Kulig; Agnieszka Olzyńska; Piotr Jurkiewicz; Anu M. Kantola; Sanna Komulainen; Moutusi Manna; Mohsen Pourmousa; Mario Vazdar; Lukasz Cwiklik; Tomasz Rog; George Khelashvili; Daniel Harries; Ville Veikko Telkki; Martin Hof; Ilpo Vattulainen; Pavel Jungwirth

doi:10.1016/j.freeradbiomed.2015.03.006

Cholesterol under oxidative stress - How lipid membranes sense oxidation as cholesterol is being replaced by oxysterols

Waldemar Kulig^*, Agnieszka Olzyńska, Piotr Jurkiewicz, Anu M. Kantola, Sanna Komulainen, Moutusi Manna, Mohsen Pourmousa, Mario Vazdar, Lukasz Cwiklik, Tomasz Rog, George Khelashvili, Daniel Harries, Ville Veikko Telkki, Martin Hof, Ilpo Vattulainen, Pavel Jungwirth

^*Corresponding author for this work

Institute of Chemistry

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

Abstract

The behavior of oxysterols in phospholipid membranes and their effects on membrane properties were investigated by means of dynamic light scattering, fluorescence spectroscopy, NMR, and extensive atomistic simulations. Two families of oxysterols were scrutinized - tail-oxidized sterols, which are mostly produced by enzymatic processes, and ring-oxidized sterols, formed mostly via reactions with free radicals. The former family of sterols was found to behave similar to cholesterol in terms of molecular orientation, roughly parallel to the bilayer normal, leading to increasing membrane stiffness and suppression of its membrane permeability. In contrast, ring-oxidized sterols behave quantitatively differently from cholesterol. They acquire tilted orientations and therefore disrupt the bilayer structure with potential implications for signaling and other biochemical processes in the membranes.

Original language	English
Pages (from-to)	30-41
Number of pages	12
Journal	Free Radical Biology and Medicine
Volume	84
DOIs	https://doi.org/10.1016/j.freeradbiomed.2015.03.006
State	Published - 1 Jul 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.All rights reserved.

Keywords

DPH anisotropy
Laurdan fluorescence
Liposomes
Molecular dynamics simulations
NMR measurements
Oxysterols
Phospholipid bilayers
Tilt modulus

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10.1016/j.freeradbiomed.2015.03.006

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Kulig, W., Olzyńska, A., Jurkiewicz, P., Kantola, A. M., Komulainen, S., Manna, M., Pourmousa, M., Vazdar, M., Cwiklik, L., Rog, T., Khelashvili, G., Harries, D., Telkki, V. V., Hof, M., Vattulainen, I., & Jungwirth, P. (2015). Cholesterol under oxidative stress - How lipid membranes sense oxidation as cholesterol is being replaced by oxysterols. Free Radical Biology and Medicine, 84, 30-41. https://doi.org/10.1016/j.freeradbiomed.2015.03.006

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abstract = "The behavior of oxysterols in phospholipid membranes and their effects on membrane properties were investigated by means of dynamic light scattering, fluorescence spectroscopy, NMR, and extensive atomistic simulations. Two families of oxysterols were scrutinized - tail-oxidized sterols, which are mostly produced by enzymatic processes, and ring-oxidized sterols, formed mostly via reactions with free radicals. The former family of sterols was found to behave similar to cholesterol in terms of molecular orientation, roughly parallel to the bilayer normal, leading to increasing membrane stiffness and suppression of its membrane permeability. In contrast, ring-oxidized sterols behave quantitatively differently from cholesterol. They acquire tilted orientations and therefore disrupt the bilayer structure with potential implications for signaling and other biochemical processes in the membranes.",

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author = "Waldemar Kulig and Agnieszka Olzy{\'n}ska and Piotr Jurkiewicz and Kantola, {Anu M.} and Sanna Komulainen and Moutusi Manna and Mohsen Pourmousa and Mario Vazdar and Lukasz Cwiklik and Tomasz Rog and George Khelashvili and Daniel Harries and Telkki, {Ville Veikko} and Martin Hof and Ilpo Vattulainen and Pavel Jungwirth",

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Kulig, W, Olzyńska, A, Jurkiewicz, P, Kantola, AM, Komulainen, S, Manna, M, Pourmousa, M, Vazdar, M, Cwiklik, L, Rog, T, Khelashvili, G, Harries, D, Telkki, VV, Hof, M, Vattulainen, I & Jungwirth, P 2015, 'Cholesterol under oxidative stress - How lipid membranes sense oxidation as cholesterol is being replaced by oxysterols', Free Radical Biology and Medicine, vol. 84, pp. 30-41. https://doi.org/10.1016/j.freeradbiomed.2015.03.006

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AU - Kulig, Waldemar

AU - Olzyńska, Agnieszka

AU - Jurkiewicz, Piotr

AU - Kantola, Anu M.

AU - Komulainen, Sanna

AU - Manna, Moutusi

AU - Pourmousa, Mohsen

AU - Vazdar, Mario

AU - Cwiklik, Lukasz

AU - Rog, Tomasz

AU - Khelashvili, George

AU - Harries, Daniel

AU - Telkki, Ville Veikko

AU - Hof, Martin

AU - Vattulainen, Ilpo

AU - Jungwirth, Pavel

PY - 2015/7/1

Y1 - 2015/7/1

N2 - The behavior of oxysterols in phospholipid membranes and their effects on membrane properties were investigated by means of dynamic light scattering, fluorescence spectroscopy, NMR, and extensive atomistic simulations. Two families of oxysterols were scrutinized - tail-oxidized sterols, which are mostly produced by enzymatic processes, and ring-oxidized sterols, formed mostly via reactions with free radicals. The former family of sterols was found to behave similar to cholesterol in terms of molecular orientation, roughly parallel to the bilayer normal, leading to increasing membrane stiffness and suppression of its membrane permeability. In contrast, ring-oxidized sterols behave quantitatively differently from cholesterol. They acquire tilted orientations and therefore disrupt the bilayer structure with potential implications for signaling and other biochemical processes in the membranes.

AB - The behavior of oxysterols in phospholipid membranes and their effects on membrane properties were investigated by means of dynamic light scattering, fluorescence spectroscopy, NMR, and extensive atomistic simulations. Two families of oxysterols were scrutinized - tail-oxidized sterols, which are mostly produced by enzymatic processes, and ring-oxidized sterols, formed mostly via reactions with free radicals. The former family of sterols was found to behave similar to cholesterol in terms of molecular orientation, roughly parallel to the bilayer normal, leading to increasing membrane stiffness and suppression of its membrane permeability. In contrast, ring-oxidized sterols behave quantitatively differently from cholesterol. They acquire tilted orientations and therefore disrupt the bilayer structure with potential implications for signaling and other biochemical processes in the membranes.

KW - DPH anisotropy

KW - Laurdan fluorescence

KW - Liposomes

KW - Molecular dynamics simulations

KW - NMR measurements

KW - Oxysterols

KW - Phospholipid bilayers

KW - Tilt modulus

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Cholesterol under oxidative stress - How lipid membranes sense oxidation as cholesterol is being replaced by oxysterols

Abstract

Bibliographical note

Keywords

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