Cell membranes provide a selective semi-permeable barrier to the passive transport of molecules. This property differs greatly between organisms. While the cytoplasmic membrane of bacterial cells is ...highly permeable for weak acids and glycerol, yeasts can maintain large concentration gradients. Here we show that such differences can arise from the physical state of the plasma membrane. By combining stopped-flow kinetic measurements with molecular dynamics simulations, we performed a systematic analysis of the permeability of a variety of small molecules through synthetic membranes of different lipid composition to obtain detailed molecular insight into the permeation mechanisms. While membrane thickness is an important parameter for the permeability through fluid membranes, the largest differences occur when the membranes transit from the liquid-disordered to liquid-ordered and/or to gel state, which is in agreement with previous work on passive diffusion of water. By comparing our results with in vivo measurements from yeast, we conclude that the yeast membrane exists in a highly ordered and rigid state, which is comparable to synthetic saturated DPPC-sterol membranes.
The nutritional value of meat is an increasingly important factor influencing consumer preferences for poultry, red meat and processed meat products. Intramuscular fat content and composition, in ...addition to high quality protein, trace minerals and vitamins are important determinants of nutritional value. Fat content of meat at retail has decreased substantially over the past 40 years through advances in animal genetics, nutrition and management and changes in processing techniques. Evidence of the association between diet and the incidence of human non-communicable diseases has driven an interest in developing production systems for lowering total SFA and trans fatty acid (TFA) content and enrichment of n-3 PUFA concentrations in meat and meat products. Typically, poultry and pork has a lower fat content, containing higher PUFA and lower TFA concentrations than lamb or beef. Animal genetics, nutrition and maturity, coupled with their rumen microbiome, are the main factors influencing tissue lipid content and relative proportions of SFA, MUFA and PUFA. Altering the fatty acid (FA) profile of lamb and beef is determined to a large extent by extensive plant and microbial lipolysis and subsequent microbial biohydrogenation of dietary lipid in the rumen, and one of the major reasons explaining the differences in lipid composition of meat from monogastrics and ruminants. Nutritional strategies can be used to align the fat content and FA composition of poultry, pork, lamb and beef with Public Health Guidelines for lowering the social and economic burden of chronic disease.
The correct funding is as follows: “Funding for this project was provided by Czech Science Foundation (Project No. 206/12/0750), Academy of Sciences of the Czech Republic (Project RVO 61388963) and ...Charles University in Prague (Project SVV 260084). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”
Nanodiscs (NDs), self-assembled lipid bilayers encircled by membrane scaffold proteins (MSPs), offer a versatile platform for the reconstitution of membrane proteins for structural and biochemical ...investigations. Saturated, isoprenoid lipids are commonly found in thermophiles and have been associated with thermotolerance. To test whether these lipids confer additional stability on ND-incorporated membrane proteins, this study focuses on the thermal stability of human cytochrome P450 3A4 (CYP3A4) inside NDs composed of different phosphocholine lipids: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC). NDs were characterized using size-exclusion chromatography coupled with multi-angle light scattering (SEC-MALS) and densitometric SDS-PAGE. CYP3A4-DPhPC-NDs were found to comprise three MSP copies instead of the canonical dimer, as reported before for the empty NDs. Rapid, thermally induced unfolding of CYP3A4 inside NDs measured using circular dichroism and differential scanning fluorimetry (nanoDSF) revealed that the CYP3A4 melting temperature was dependent on ND composition. In POPC and DMPC-CYP3A4-NDs the melting temperature was comparable to CYP3A4 without NDs (59 °C). CYP3A4 in DPhPC-NDs showed an increase in melting temperature of 4 °C. Decline in CYP3A4 integrity as well as ND aggregation and disintegration occur at similar rates for all membrane types when subjected to exposure at 37 °C for several hours. The POPC and DMPC- CYP3A4-NDs show significant lipid loss over time, which is not observed for DPhPC-NDs. The results demonstrate that thermally induced denaturation of protein-NDs is a complex, multifaceted process, which is not represented well by rapid thermal unfolding experiments.
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•Phytanyl chain Nanodiscs contain three scaffold proteins, offering accessible lipid area for membrane protein reconstitution.•Cytochrome P450 3A4 has a higher melting temperature in phytanyl Nanodiscs than in Nanodiscs containing linear acyl lipids.•Nanodisc thermal stability was measured over time using orthogonal techniques to assess constituent fates and stability.
Cancer cells are often exposed to a metabolically challenging environment with scarce availability of oxygen and nutrients. This metabolic stress leads to changes in the balance between the ...endogenous synthesis and exogenous uptake of fatty acids, which are needed by cells for membrane biogenesis, energy production and protein modification. Alterations in lipid metabolism and, consequently, lipid composition have important therapeutic implications, as they affect the survival, membrane dynamics and therapy response of cancer cells. In this article, we provide an overview of recent insights into the regulation of lipid metabolism in cancer cells under metabolic stress and discuss how this metabolic adaptation helps cancer cells thrive in a harsh tumour microenvironment.
Lipids and Alzheimer's Disease Kao, Yu-Chia; Ho, Pei-Chuan; Tu, Yuan-Kun ...
International journal of molecular sciences,
02/2020, Letnik:
21, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Lipids, as the basic component of cell membranes, play an important role in human health as well as brain function. The brain is highly enriched in lipids, and disruption of lipid homeostasis is ...related to neurologic disorders as well as neurodegenerative diseases such as Alzheimer's disease (AD). Aging is associated with changes in lipid composition. Alterations of fatty acids at the level of lipid rafts and cerebral lipid peroxidation were found in the early stage of AD. Genetic and environmental factors such as apolipoprotein and lipid transporter carrying status and dietary lipid content are associated with AD. Insight into the connection between lipids and AD is crucial to unraveling the metabolic aspects of this puzzling disease. Recent advances in lipid analytical methodology have led us to gain an in-depth understanding on lipids. As a result, lipidomics have becoming a hot topic of investigation in AD, in order to find biomarkers for disease prediction, diagnosis, and prevention, with the ultimate goal of discovering novel therapeutics.
Ferroptosis is a recently identified form of regulated cell death defined by the iron-dependent accumulation of lipid reactive oxygen species. Ferroptosis has been studied in various diseases such as ...cancer, Parkinson's disease, and stroke. However, the exact function and mechanism of ferroptosis in ischemia/reperfusion (I/R) injury, especially in the intestine, remains unknown. Considering the unique conditions required for ferroptosis, we hypothesize that ischemia promotes ferroptosis immediately after intestinal reperfusion. In contrast to conventional strategies employed in I/R studies, we focused on the ischemic phase. Here we verified ferroptosis by assessing proferroptotic changes after ischemia along with protein and lipid peroxidation levels during reperfusion. The inhibition of ferroptosis by liproxstatin-1 ameliorated I/R-induced intestinal injury. Acyl-CoA synthetase long-chain family member 4 (ACSL4), which is a key enzyme that regulates lipid composition, has been shown to contribute to the execution of ferroptosis, but its role in I/R needs clarification. In the present study, we used rosiglitazone (ROSI) and siRNA to inhibit ischemia/hypoxia-induced ACSL4 in vivo and in vitro. The results demonstrated that ACSL4 inhibition before reperfusion protected against ferroptosis and cell death. Further investigation revealed that special protein 1 (Sp1) was a crucial transcription factor that increased ACSL4 transcription by binding to the ACSL4 promoter region. Collectively, this study demonstrates that ferroptosis is closely associated with intestinal I/R injury, and that ACSL4 has a critical role in this lethal process. Sp1 is an important factor in promoting ACSL4 expression. These results suggest a unique and effective mechanistic approach for intestinal I/R injury prevention and treatment.
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•The lipid changes of bigeye tuna (Thunnus obesus) during cold storage were studied.•136 PC and 64 PE molecular species were identified in bigeye tuna.•TAG and PL particles ...significantly decreased by CLSM and LC-MS/MS.
This study aimed to investigate the lipid oxidation and distribution in Bigeye tuna stored at 0 °C and 4 °C for 6 days. Tuna were evaluated by determining the peroxide value (POV), acid value (AV), anisidine value (AnV), polyene index, fluorescence ratio (FR), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) content, and major glycerophospholipid molecular species. The value of lipid oxidation indexes (POV, AV, AnV, FR, PC, PE and PI) increased as the storage time increased. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) results indicated that the major types of lipids included diacylglycerol (DAG), monoacylglycerol (MAG), phospholipid (PL), and triacylglycerol (TAG). At least 136 PC and 64 PE molecular species were identified in Bigeye tuna. The results of the confocal laser scanning microscope analysis indicated the distribution of TAG and PL particles. In addition, principal component analysis showed that the contents of PI and TAG were positively correlated with PC, polyene index and lipid content but negatively correlated with PI, POV, FR, AOV, AnV, MAG, and DAG, which might be explained by distinguishing the lipid parameters affecting lipid oxidation. Therefore, this study may provide a novel method to evaluate lipid changes and contribute to the balanced nutritional value of aquatic foods during cold storage.
Biological membranes are key elements for the maintenance of cell architecture and physiology. Beyond a pure barrier separating the inner space of the cell from the outer, the plasma membrane is a ...scaffold and player in cell-to-cell communication and the initiation of intracellular signals among other functions. Critical to this function is the plasma membrane compartmentalization in lipid microdomains that control the localization and productive interactions of proteins involved in cell signal propagation. In addition, cells are divided into compartments limited by other membranes whose integrity and homeostasis are finely controlled, and which determine the identity and function of the different organelles. Here, we review current knowledge on membrane lipid composition in the plasma membrane and endomembrane compartments, emphasizing its role in sustaining organelle structure and function. The correct composition and structure of cell membranes define key pathophysiological aspects of cells. Therefore, we explore the therapeutic potential of manipulating membrane lipid composition with approaches like membrane lipid therapy, aiming to normalize cell functions through the modification of membrane lipid bilayers.
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