Phase separation is induced by phenothiazine derivatives in phospholipid/sphingomyelin/cholesterol mixtures containing low levels of cholesterol and sphingomyelin

Abstract

. Phase separation is induced by phenothiazine derivatives in phospholipid/sphingomyelin/cholesterol mixtures containing low levels of cholesterol and sphingomyelin. Biophysical Chemistry, Elsevier, 2007, 130 (1-2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In the present work differential scanning calorimetry and fluorescence spectroscopy with the use of Laurdan probe was employed to demonstrate the existence of phase separation in model systems containing DPPC with addition of 5 mol% or 10 mol% of both cholesterol and sphingomyelin. Additionally, the influence of three phenothiazine derivatives on phase separation in mixed DPPC/cholesterol/sphingomyelin bilayers was investigated. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPTChlorpromazine, thioridazine and trifluoperazine were able to induce phase separation in DPPC and DPPC/cholesterol/sphingomyelin bilayers in temperatures below lipid main phase transition. However, only trifluoperazine induced phase separation in temperatures close to or above main phase transition. Trifluoperazine also induced phase separation in bilayers composed of egg yolk PC or DOPC mixed with cholesterol and sphingomyelin. We concluded that presence of lipid domains can be observed in model membranes containing low levels of cholesterol and sphingomyelin. Among three phenothiazine derivatives studied, only trifluoperazine was able to induce a permanent phase separation in phosphatidylcholine/cholesterol/sphingomyelin systems.

Modification of membrane heterogeneity by antipsychotic drugs: An X-ray diffraction comparative study

“…CPZ/cholesterol interchange at the condensed complexed level is proposed to account for the Lo thickness decrease. This interchange hypothesis is also suggested by an experiment in which CPZ is added to a mixture where cholesterol is under a concentration inducing a phase separation: CPZ addition to a ternary mixture made of DPPC, low SM and cholesterol was able to induce a phase separation [19]. Such mechanism can be involved for all studied AP as suggested by our results showing that all AP compounds except from AMI were inducing a Lo bilayer thickness decrease.…”

Binding Ability of Lacosamide to Phosphatidylcholine Lipids and Cholesterol Effects

“…ΔH and Tm); FT-IR spectroscopy offers data about lipid dynamics (fluidity), lipid acyl chain flexibility (ordering), hydration state. Thus, these techniques have been extensively utilized in these kinds of works 13,[17][18][19]22,[24][25][26][27][28] .…”

“…In order to bring more clarification to this issue, wavenumber values of C=O and PO 2 -symmetric stretching bands were evaluated within the scope of the present study. The C=O mode is attributed to the carbonyl groups of the glycerol backbone near hydrophilic region while PO 2 -band is assigned to head groups of lipids 13,17,22,[24][25][26][27] . Due to their chemical features both LCM and CHO are expected to interact with such groups over hydrogen bonding.…”

“…It is very well-known that when drug molecules interact with membrane lipids, biophysical parameters of lipids such as phase transition enthalpy (ΔH), phase transition temperature (Tm), lipid order, lipid fluidity and hydrogen state of glycerol and phosphate groups are changed. By monitoring such changes in model membrane systems the information about the degree of interaction and behaviour of the drug in real membrane systems can be obtained 14,17,[26][27] . Similarly, in the present study we aimed to provide information for binding ability of LCM with PC membrane lipids, and designed our experiments on a well-established molecular models of biomembranes 13,18,22,24,26 , multilamellar vesicles (MLVs) formed by DPPC and CHO lipids, as similarly performed for phenytoin, 12 and gabapentin and levetricetam 13 .…”

“…Indeed, in the absence and the presence of CHO (10 mol%), the effects of LCM at different concentrations (1-10-20 mol%) on biophysical parameters of DPPC MLVs were investigated. To achieve this, Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) were utilized as in earlier studies 12,13,[17][18][19]22,[24][25][26][27] .…”