Wnętrzak Anita, Makyła-Juzak Katarzyna, Filiczkowska Anna, Kulig Waldemar, Dynarowicz-Łątka Patrycja
Jagiellonian University, Ingardena 3, 30-060, Krakow, Poland.
Institute of Physics, Jagiellonian University, Łojasiewicza 11, 30-348, Krakow, Poland.
J Membr Biol. 2017 Oct;250(5):553-564. doi: 10.1007/s00232-017-9984-8. Epub 2017 Aug 31.
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.
氧化甾醇是胆固醇氧化的产物。它们可以在体内（通过酶促和非酶促反应）以及体外（随食物摄入）形成。最近的研究清楚地证明了这些化合物的细胞毒性特性，主要是由于它们掺入天然脂质双层中。这个过程会影响生物膜的机械和物理化学性质，主要是通过改变其成分之间的相互作用，这可能导致细胞膜正常功能的破坏，并可能导致其降解。因此，可以假设氧化甾醇可能会影响神经退行性疾病的发生，包括阿尔茨海默病。然而，这些分子在分子水平上的作用方式尚不完全清楚。为了更好地理解氧化甾醇在神经退行性变中的作用，研究氧化甾醇与神经元膜成分之间的相互作用非常重要。可以用来分析这种相互作用的最有前途的技术之一是朗缪尔单分子层技术。在这项工作中，我们制备了一种人工神经元膜，将其模拟为由胆固醇、1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱（POPC）和鞘磷脂（SM）组成的多组分朗缪尔单分子层。为了研究在氧化应激下膜性质是否有任何变化，在本文中我们研究了代表性的环氧化氧化甾醇：7-酮胆固醇（7-KC）的影响。我们的结果表明，用7-KC替代胆固醇会增加模型膜中分子之间的相互作用。
