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

Kulig, Waldemar; Olżyńska, Agnieszka; Jurkiewicz, Piotr; Kantola, Anu M.; Komulainen, Sanna; Manna, Moutusi; Pourmousa, Mohsen; Vazdar, Mario; Ćwiklik, Łukasz; Róg, Tomasz; Khelashvili, George; Harries, Daniel; Telkki, Ville‐Veikko; Hof, Martin; Vattulainen, Ilpo; Jungwirth, Pavel

doi:10.1016/j.freeradbiomed.2015.03.006

Cited by 66 publications

(96 citation statements)

References 91 publications

(95 reference statements)

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“…Rather, some hydroxysterols caused a small decrease of lipid chain order. A similar tendency was observed for 24 S -HC also using 2 H NMR measurements [21]. This membrane behavior of the hydroxycholesterols can be rationalized in that the additional hydroxy moiety in these molecules diminishes their interaction with surrounding phospholipids.…”

Section: Discussionsupporting

confidence: 77%

“…So far, only slightly altered lipid mobility was observed in the presence of both hydroxysterols using fluorescence techniques [21]. Also, a decreased but still significant effect of the hydroxysterols on lipid condensation compared to native cholesterol was found in molecular dynamics simulations, which is probably caused by an increased tilt angle of the sterols to the membrane normal [8,21]. However, using 2 H NMR measurements, only a very small increase of acyl chain order was observed in the presence of 24 S -HC [8].…”

Section: Introductionmentioning

confidence: 99%

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Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

Hilsch

Haralampiev

Müller

et al. 2017

Beilstein J. Org. Chem.

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Compared to cholesterol, hydroxycholesterols contain an additional hydroxy group in the alkyl chain and are able to efficiently cross the brain-blood barrier. Therefore, they are responsible for the sterol transfer between brain and circulation. The current study compares the membrane properties of several hydroxycholesterols with those of cholesterol using 2 H NMR spectroscopy, a membrane permeability assay, and fluorescence microscopy experiments. It is shown that hydroxycholesterols do not exert the unique impact on membrane properties characteristic for cholesterol with regard to the influence on lipid chain order, membrane permeability and formation of lateral domains. 720

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

Hilsch

Haralampiev

Müller

et al. 2017

Beilstein J. Org. Chem.

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“…As compared to cholesterol, CHS is a more water-soluble cholesterol ester and is widely used in structural biology and biophysical studies as a cholesterol analogue (Zocher et al, 2012; Loll, 2014). Oxysterols, on the other hand, are derivatives of cholesterol with additional oxygen-containing substitutions at different positions of cholesterol (Olkkonen and Hynynen, 2009; Kulig et al, 2015a; Neuvonen et al, 2014). Due to the structural similarities with cholesterol, these analogues mimic cholesterol as to the effects on membrane properties (e.g., increasing bilayer order and thickness), although to different extents (Figure 2—figure supplement 6) (Kulig et al, 2015a, 2015b).…”

Section: Resultsmentioning

confidence: 99%

“…The all-atom OPLS-AA (optimized potentials for liquid simulations) force field was used to parameterize the protein, ions, and pyrene (Jorgensen et al, 1996; Kaminski et al, 2001). Force field parameters for cholesterol, cholesteryl hemisuccinate, and oxysterols were taken from previously published papers (Manna et al, 2015; Kulig et al, 2015a, 2015b, 2014). For the studied phosphatidylcholines (DOPC and PC-20:0/22:1 c13), we used new torsional and Lennard-Jones parameters derived for saturated (Maciejewski et al, 2014) and unsaturated hydrocarbons (Kulig et al, 2015c, 2016) and the torsional potential developed for the glycerol backbone and the phosphatidylcholine head group (Maciejewski et al, 2014).…”

Section: Methodsmentioning

confidence: 99%

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Mechanism of allosteric regulation of β2-adrenergic receptor by cholesterol

Manna

Niemelä

Tynkkynen

et al. 2016

eLife

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121

133

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There is evidence that lipids can be allosteric regulators of membrane protein structure and activation. However, there are no data showing how exactly the regulation emerges from specific lipid-protein interactions. Here we show in atomistic detail how the human β2-adrenergic receptor (β2AR) – a prototypical G protein-coupled receptor – is modulated by cholesterol in an allosteric fashion. Extensive atomistic simulations show that cholesterol regulates β2AR by limiting its conformational variability. The mechanism of action is based on the binding of cholesterol at specific high-affinity sites located near the transmembrane helices 5–7 of the receptor. The alternative mechanism, where the β2AR conformation would be modulated by membrane-mediated interactions, plays only a minor role. Cholesterol analogues also bind to cholesterol binding sites and impede the structural flexibility of β2AR, however cholesterol generates the strongest effect. The results highlight the capacity of lipids to regulate the conformation of membrane receptors through specific interactions.DOI: http://dx.doi.org/10.7554/eLife.18432.001

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Dietary (poly)phenols as modulators of the biophysical properties in endothelial cell membranes: its impact on nitric oxide bioavailability in hypertension

Reis,

Rocha,

Laranjinha

et al. 2024

FEBS Letters

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Hypertension is a major contributor to premature death, owing to the associated increased risk of damage to the heart, brain and kidneys. Although hypertension is manageable by medication and lifestyle changes, the risk increases with age. In an increasingly aged society, the incidence of hypertension is escalating, and is expected to increase the prevalence of (cerebro)vascular events and their associated mortality. Adherence to plant‐based diets improves blood pressure and vascular markers in individuals with hypertension. Food flavonoids have an inhibitory effect towards angiotensin‐converting enzyme (ACE1) and although this effect is greatly diminished upon metabolization, their microbial metabolites have been found to improve endothelial nitric oxide synthase (eNOS) activity. Considering the transmembrane location of ACE1 and eNOS, the ability of (poly)phenols to interact with membrane lipids modulate the cell membrane's biophysical properties and impact on nitric oxide (·NO) synthesis and bioavailability, remain poorly studied. Herein, we provide an overview of the current knowledge on the lipid remodeling of endothelial membranes with age, its impact on the cell membrane's biophysical properties and ·NO permeability across the endothelial barrier. We also discuss the potential of (poly)phenols and other plant‐based compounds as key players in hypertension management, and address the caveats and challenges in adopted methodologies.

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

Cited by 66 publications

References 91 publications

Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

Mechanism of allosteric regulation of β2-adrenergic receptor by cholesterol

Dietary (poly)phenols as modulators of the biophysical properties in endothelial cell membranes: its impact on nitric oxide bioavailability in hypertension

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