Lipocarbazole, an efficient lipid peroxidation inhibitor anchored in the membrane

Fabre, Gabin; Hänchen, Anne; Calliste, Claude-Alain; Berka, Karel; Banala, Srinivas; Otyepka, Michal; Süssmuth, Roderich D.; Trouillas, Patrick

doi:10.1016/j.bmc.2015.05.031

Cited by 13 publications

(6 citation statements)

References 41 publications

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“…This lipid bilayer was solvated with 3314 water molecules and was made of 64 DPPC molecules per layer, neutralized with sodium and chlorine ions. The size of the lipid bilayer has been found to be big enough to be representative of the actual system, as previously reported. − The system is considered equilibrated when the transition dipole moment has negligible fluctuations in orientation, which translates into an equilibration time of 240 ns for Conf-I and 200 ns for Conf-II. Partial charges of the probes in vacuum have been obtained with the electrostatic potential (ESP) scheme as implemented in the Gaussian 09 suite of programs .…”

Section: Methodsmentioning

confidence: 75%

Conformational Changes as Driving Force for Phase Recognition: The Case of Laurdan

et al. 2019

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The development of a universal probe to assess the phase of a lipid membrane is one of the most ambitious goals for fluorescence spectroscopy. The ability of a well-known molecule as Laurdan to reach this aim is here exploited as the behavior of the probe is fully characterized in a dipalmitoylphosphatidylcholine (DPPC) solid gel (So) phase by means of molecular dynamics simulations. Laurdan can take two conformations, depending on whether the carbonyl oxygen points toward the β-position of the naphthalene core (Conf-I) or to the α-position (Conf-II). We observe that Conf-I has an elongated form in this environment, whereas Conf-II takes an Lshape. Interestingly, our theoretical calculations show that these two conformations behave in an opposite way from what is reported in the literature for a DPPC membrane in a liquid disordered (Ld) phase, where Conf-I assumes an L-shape and Conf-II is elongated. Moreover, our results show that in DPPC (So) no intermixing between the conformations is present, whereas it has been seen in a fluid environment such as DOPC (Ld). Through a careful analysis of angle distributions and by means of the rotational autocorrelation function, we predict that the two conformers of Laurdan behave differently in different membrane environments.

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Section: Methodsmentioning

confidence: 75%

Conformational Changes as Driving Force for Phase Recognition: The Case of Laurdan

et al. 2019

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“…The role of the hydroxyl group in free radical scavenging was also previously underlined for numerous polyphenols (62)(63)(64)(65) and by Fabre et al (66), who studied lipocarbazole derivatives and their location and orientation in lipid bilayers. Similarly, the study conducted by Á lvarez-Diduk et al (67), who examined N-acetylserotonin ROS scavenging capacity, substantiates the importance of the hydroxyl group.…”

Section: Antioxidant Properties and Molecular Structure Of Serotoninmentioning

confidence: 75%

Antioxidant and Membrane Binding Properties of Serotonin Protect Lipids from Oxidation

Azouzi

Santuz

Morandat

et al. 2017

Biophysical Journal

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Serotonin (5-hydroxytryptamine, 5-HT) is a well-known neurotransmitter that is involved in a growing number of functions in peripheral tissues. Recent studies have shown nonpharmacological functions of 5-HT linked to its chemical properties. Indeed, it was reported that 5-HT may, on the one hand, bind lipid membranes and, on the other hand, protect red blood cells through a mechanism independent of its specific receptors. To better understand these underevaluated properties of 5-HT, we combined biochemical, biophysical, and molecular dynamics simulations approaches to characterize, at the molecular level, the antioxidant capacity of 5-HT and its interaction with lipid membranes. To do so, 5-HT was added to red blood cells and lipid membranes bearing different degrees of unsaturation. Our results demonstrate that 5-HT acts as a potent antioxidant and binds with a superior affinity to lipids with unsaturation on both alkyl chains. We show that 5-HT locates at the hydrophobic-hydrophilic interface, below the glycerol group. This interfacial location is stabilized by hydrogen bonds between the 5-HT hydroxyl group and lipid headgroups and allows 5-HT to intercept reactive oxygen species, preventing membrane oxidation. Experimental and molecular dynamics simulations using membrane enriched with oxidized lipids converge to further reveal that 5-HT contributes to the termination of lipid peroxidation by direct interaction with active groups of these lipids and could also contribute to limit the production of new radicals. Taken together, our results identify 5-HT as a potent inhibitor of lipid peroxidation and offer a different perspective on the role of this pleiotropic molecule.

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“…Preparation of the membranes has been specified in detail elsewhere . A box of 128 lipids in periodic boundary conditions has previously been found to be largely sufficient to prevent an interaction of the DiD dye with itself, − and an analogous routine has been found to thoroughly describe and explain the experimental UV/vis spectra of vitamins E and C and quercetin in a DOPC membrane . Na + and Cl – ions were added to bulk water at a physiological concentration (0.9%) .…”

Section: Methodsmentioning

confidence: 99%

Combining (Non)linear Optical and Fluorescence Analysis of DiD To Enhance Lipid Phase Recognition

Osella

Meo

Murugan

et al. 2018

J. Chem. Theory Comput.

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The widespread interest in phase recognition of lipid membranes has led to the use of different optical techniques to enable differentiation of healthy and not fully functional cells. In this work, we show how the combination of different (non)linear optical methods such as one-photon absorption (OPA), two-photon absorption (TPA), and second harmonic generation (SHG) as well as the study of the fluorescence decay time leads to an enhanced screening of membrane phases using a fluorescent 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiD) probe. In the current study we consider the pure liquid disordered phases of DOPC (dioleoyl- sn-glycero-3-phosphocholine, room temperature) and DPPC (1,2-dipalmitoyl- sn-glycero-3-phosphocholine, 323 K), the solid gel phase of DPPC (298 K), and the liquid ordered phase of a 2:1 binary mixture of sphingomyelin and cholesterol. By means of extensive hybrid quantum mechanics-molecular mechanics calculations and based upon the (non)linear absorption of the embedded probes, it is found that DiD can be used to identify the lipid bilayer phase. The joint TPA and SHG as well as fluorescence analyses qualifies DiD as a versatile probe for phase recognition. In particular, the SHG data obtained by means of hyper-Rayleigh scattering and by electric field induced second harmonic generation reveal differences in polarization of the probe in the different environments. The TPA results finally confirm the particular location of the probe in between the polar headgroup region of the 2:1 SM:Chol mixture in the liquid ordered phase.

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Lipocarbazole, an efficient lipid peroxidation inhibitor anchored in the membrane

Cited by 13 publications

References 41 publications

Conformational Changes as Driving Force for Phase Recognition: The Case of Laurdan

Conformational Changes as Driving Force for Phase Recognition: The Case of Laurdan

Antioxidant and Membrane Binding Properties of Serotonin Protect Lipids from Oxidation

Combining (Non)linear Optical and Fluorescence Analysis of DiD To Enhance Lipid Phase Recognition

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