Oxidized glycerophosphocholines
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Lipid oxidation is one of the most important processes occurring in living cells and has been investigated through stable end-products. Currently, new insights into many physiological and pathophysiological processes provide a measurement of the first products of oxidation, e.g., oxidized glycerophosphatidylcholines (oxGPCs). Here, we evaluate the capacity of untargeted global metabolomics to measure oxGPCs in serum samples. This evaluation covered analytical reproducibility and data quality as well as the ability to capture metabolic alterations in diverse conditions. The analytical evaluation was performed based on the quality control samples, while the comparative analysis was based on the model of the development of type 2 diabetes mellitus (T2DM). The novelty of this approach arises not only from the measurement of oxGPCs instead of lipid peroxide-derived aldehydes but also from the stratification of the patients according to body mass index (BMI). Such a scenario was dictated by the fact that, despite the well-known relationship between obesity and T2DM development, there are lean individuals suffering from T2DM as well as obese people with normal glucose homeostasis. Our results provided evidence to support the ability of nontargeted metabolomics to measure oxGPCs. Comparative analysis of measured oxGPCs revealed differences in the level of oxGPCs either between different stages of disease development (insulin resistance, prediabetes) or BMI groups (normal weight, overweight, obese). The obtained results provided new insights into the metabolic processes leading to the development of T2DM and opened new paths in the investigation of the impact of body mass in T2DM progress.
- MeSH
- chromatografie kapalinová MeSH
- diabetes mellitus 2. typu krev metabolismus MeSH
- dospělí MeSH
- glycerylfosforylcholin krev chemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolom fyziologie MeSH
- metabolomika metody MeSH
- oxidace-redukce MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Fluidity of lipid membranes is known to play an important role in the functioning of living organisms. The fluorescent probe Laurdan embedded in a lipid membrane is typically used to assess the fluidity state of lipid bilayers by utilizing the sensitivity of Laurdan emission to the properties of its lipid environment. In particular, Laurdan fluorescence is sensitive to gel vs liquid⁻crystalline phases of lipids, which is demonstrated in different emission of the dye in these two phases. Still, the exact mechanism of the environment effects on Laurdan emission is not understood. Herein, we utilize dipalmitoylphosphatidylcholine (DPPC) and dioleoylphosphatidylcholine (DOPC) lipid bilayers, which at room temperature represent gel and liquid⁻crystalline phases, respectively. We simulate absorption and emission spectra of Laurdan in both DOPC and DPPC bilayers with quantum chemical and classical molecular dynamics methods. We demonstrate that Laurdan is incorporated in heterogeneous fashion in both DOPC and DPPC bilayers, and that its fluorescence depends on the details of this embedding.
- MeSH
- 1,2-dipalmitoylfosfatidylcholin chemie MeSH
- 2-naftylamin analogy a deriváty chemie MeSH
- chemické modely * MeSH
- fluorescence MeSH
- fosfatidylcholiny chemie MeSH
- kvantová teorie MeSH
- laurany chemie MeSH
- lipidové dvojvrstvy chemie MeSH
- simulace molekulární dynamiky * MeSH
- Publikační typ
- časopisecké články MeSH
Different models of phospholipid membranes (PLMs) have been utilized for better understanding of properties and functionality of real biological membranes. Mechanisms of transport processes and membrane properties can be investigated on planar phospholipid bilayers. Electrochemical behavior of phosphatidylcholine-cholesterol mixtures in the PLM form was studied by electrochemical impedance spectroscopy. Phosphatidylcholine (lecithin) and cholesterol are essential for living cells and, therefore, they were chosen for experiments. Different lecithin/cholesterol ratios were tested on different polycarbonate(PC). This material is formed by a condensation polyme¬rization resulting in a carbon that is bonded to three oxygens. The time dependence of PLM formation in the presence of cholesterol was investigated.
- MeSH
- 1,2-dipalmitoylfosfatidylcholin chemie MeSH
- buněčná membrána MeSH
- cholesterol chemie MeSH
- elektrochemické techniky metody přístrojové vybavení využití MeSH
- elektrochemie * MeSH
- fluidita membrány MeSH
- impedanční spektroskopie * metody přístrojové vybavení využití MeSH
- lecitiny chemie MeSH
- lipidové dvojvrstvy * MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- 1,2-dipalmitoylfosfatidylcholin * MeSH
- absorpce * MeSH
- antioxidancia MeSH
- buněčná membrána MeSH
- ethanol * MeSH
- kyselina askorbová * MeSH
- lidé MeSH
- ochranné látky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic experimental techniques due to their small size, yet there is also a lack of atomistic simulation models able to describe spontaneous nanodomain formation in sufficiently simple but biologically relevant complex membranes. Here we use atomistic simulations to consider a binary mixture of saturated dipalmitoylphosphatidylcholine and cholesterol - the "minimal standard" for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets. The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip-flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains. The model considered explains a plethora of controversial experimental results and provides an excellent basis for further computational studies on nanodomains. Furthermore, the results highlight the role of cholesterol as a key player in the modulation of nanodomains for membrane protein function.
To elucidate the consequences of the saturated-unsaturated nature of lipid surface films, monolayers formed by an equimolar mixture of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipids are investigated in a wide range of surface pressures. As such mixtures share some features with naturally-occurring surfactants, for example the lung surfactant, the systems are studied at the temperature relevant for human body. All-atom molecular dynamics simulations and Langmuir trough experiments are employed. The binary lipid mixture is compared with the corresponding one-component systems. Atomistic-level alterations of monolayer molecular properties upon lateral compression are scrutinized. These involve elevation of lateral ordering of lipid chains, modulation of chain and headgroup orientation, and reduction of lipid hydration. The presence of the unsaturated POPC in the DPPC/POPC mixture reduces the liquid expanded-liquid condensed coexistence region and moderates the phase transition. Simulations predict that nanoscale lipid de-mixing occurs with small transient DPPC clusters emerging due to local fluctuations of the lateral lipid arrangement. A vertical sorting of lipids induced by lateral compression is also observed, with DPPC transferred toward the water phase. Both the conformational lipid alterations due to monolayer compression as well as the existence of lateral dynamic inhomogeneities of the lipid film are potentially pertain to dynamic and non-homogeneous lipid interfacial systems.
