Oxysterols Versus Cholesterol in Model Neuronal Membrane. I. The Case of 7-Ketocholesterol. The Langmuir Monolayer Study

Abstract

Oxysterols are products of cholesterol oxidation. They can be formed endogenously (in both enzymatic and non-enzymatic reactions) as well as exogenously (delivered with food). Recent studies clearly demonstrate cytotoxic properties of these compounds, being mainly due to their incorporation into natural lipid bilayers. This process can influence mechanical and physicochemical properties of biomembrane—mainly by modifying the interactions between its components, which may result in the disruption of proper functioning of cell membrane and could lead to its degradation. Therefore, it can be assumed that oxysterols may affect the initiation of neurodegenerative diseases, including Alzheimer’s disease. However, the mode of action of these molecules at the molecular level is not fully known. To get a better understanding of the role of oxysterols in neurodegeneration, it is of great importance to examine mutual interactions between oxysterols and neuronal membrane components. One of the most promising techniques that can be used to analyze such interactions is the Langmuir monolayer technique. In this work, we have prepared an artificial neuronal membrane modeled as multicomponent Langmuir monolayer built up with cholesterol, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and sphingomyelin (SM). To examine whether there are any changes in the membrane properties under oxidative stress, in this paper we have investigated the impact of the representative ring-oxidized oxysterol: 7-ketocholesterol (7-KC). Our results show that replacing cholesterol with 7-KC increases the interaction between molecules in the model membrane.Electronic supplementary materialThe online version of this article (doi:10.1007/s00232-017-9984-8) contains supplementary material, which is available to authorized users.

Electrical Properties of Membrane Phospholipids in Langmuir Monolayers

“…The results of surface pressure ( ) and electric surface potential changes ( ) versus area per molecule ( ) measurements for the investigated lipids are presented in Figure 1 and Figure 2 . Experimental isotherms for all the studied phospholipids are in good agreement with those already published ([ 33 ] for DPPC, [ 34 ] for DSPC, [ 35 ] for DAPC, [ 36 ] for DOPC, [ 37 ] for DPPE and [ 38 ] for SM). Experimental curves can be characterized by two important parameters: critical area ( , which corresponds to the area at which is triggered off) and maximum value of surface potential ( ).…”

Lipids in the Physiopathology of Hereditary Spastic Paraplegias

“…Oxysterols are present at very low levels compared to cholesterol (Wnętrzak et al, 2017), and alterations of cholesterol synthesis or trafficking are induced by the loss of function of several genes responsible for HSP. For example, loss of function of Erlin1 and Erlin2, mutated in SPG62 and SPG18, respectively, are responsible for early onset autosomal recessive HSP associated with cognitive impairment (Alazami et al, 2011;Novarino et al, 2014).…”

Site of the Hydroxyl Group Determines the Surface Behavior of Bipolar Chain-Oxidized Cholesterol Derivatives─Langmuir Monolayer Studies Supplemented with Theoretical Calculations

“…Additionally, synthetic 24­( R )-OH is at least 1 order of magnitude less active compared to the natural isomer . Previous investigations involving oxysterols revealed that not only the kind of an additional polar group introduced into the cholesterol backbone , but also its position in the sterane system or chain and molecule orientation , strongly effect oxysterol organization at the phase boundary and modify the interactions with other lipids. This may directly impact the membranous activity of oxysterols as well as their other biological properties.…”