Chemistry and Physics of Lipids最新文献_第4页

Decoding the Lipid-POI connection: The mediating role of inflammatory factors 解码脂质- poi连接：炎症因子的中介作用

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids

Pub Date : 2025-05-03 DOI: 10.1016/j.chemphyslip.2025.105495

Tingyu Lang , Shaoqi Hua , Xiaolei Liang , Yongxiu Yang

POI is a highly heterogeneous, multifactorial condition, and dysregulated lipid metabolism has been implicated in its inflammatory pathogenesis This study is the first to systematically investigate causal relationships between 179 lipid species, 91 inflammatory factors, and POI using Two-Sample Mendelian Randomization (TSMR) and Multivariable Mendelian Randomization (MVMR). By integrating lipidomics and inflammatories data with POI from Genome-wide association study (GWAS) and FinnGen, we identified 18 causally significant lipids, including risk-elevating phosphatidylcholines and sphingomyelins, and protective triglycerides. Methodologically, we innovatively applied Bayesian Weighted Mendelian Randomization (BWMR) to confirm the robustness of causal estimates, addressing limitations of conventional MR in pleiotropy-prone metabolic networks. Biologically, we discovered IL-10 mediates 7.02–9.03 % of the effects of sphingomyelin (d40:2) and (d42:2) on POI, reconciling lipid-driven inflammation with ovarian aging—a mechanism previously unreported. Sensitivity analyses confirmed no horizontal pleiotropy (p > 0.05). This work establishes three advances: (1) First MR evidence linking specific lipid subclasses (not just broad categories) to POI; (2) Identification of IL-10 as a novel inflammatory mediator bridging sphingolipids and POI pathogenesis; (3) A validated framework combining MVMR and mediation analysis to disentangle direct/indirect effects in reproductive aging. Our findings provide clinically actionable insights: IL-10 emerge as potential biomarkers, while triglycerides highlight dietary/therapeutic targets. This mechanistic clarity advances POI research beyond prior observational associations into causal biology.

POI是一种高度异质性、多因素的疾病，脂质代谢失调与其炎症发病机制有关。本研究首次采用双样本孟德尔随机化（TSMR）和多变量孟德尔随机化（MVMR）系统地研究了179种脂质、91种炎症因子与POI之间的因果关系。通过整合来自全基因组关联研究（GWAS）和FinnGen的脂质组学和炎症数据，我们确定了18种具有因果意义的脂质，包括风险升高的磷脂酰胆碱和鞘磷脂，以及保护性甘油三酯。在方法上，我们创新地应用贝叶斯加权孟德尔随机化（BWMR）来确认因果估计的稳健性，解决了传统MR在多向性倾向代谢网络中的局限性。生物学上，我们发现IL-10介导鞘磷脂（d40:2）和鞘磷脂（d42:2）对POI的影响的7.02-9.03 %，调和脂质驱动的炎症和卵巢老化-这是一种以前未报道的机制。敏感性分析证实无水平多效性（p >； 0.05）。这项工作建立了三个进展：(1)第一个磁共振证据将特定的脂质亚类（不仅仅是宽泛的类别）与POI联系起来；(2) IL-10作为连接鞘脂和POI发病机制的新型炎症介质的鉴定；(3)结合MVMR和中介分析的验证框架来理清生殖老龄化的直接/间接影响。我们的研究结果提供了临床可操作的见解：IL-10成为潜在的生物标志物，而甘油三酯则突出了饮食/治疗靶点。这种机制的清晰性使POI研究超越了先前的观察关联，进入因果生物学。

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引用次数: 0

Cholesterol´s role in membrane organization and nicotinic acetylcholine receptor function: Implications for aging and Alzheimer's disease 胆固醇在膜组织和尼古丁乙酰胆碱受体功能中的作用：对衰老和阿尔茨海默病的影响。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids

Pub Date : 2025-03-25 DOI: 10.1016/j.chemphyslip.2025.105484

Daniel A. Peñalva, Juan Pablo Munafó, Silvia S. Antollini

Biological membranes are complex entities composed of various molecules exhibiting lateral and transbilayer lipid asymmetries, along with a selective spatial distribution of different membrane proteins. This dynamic orchestration is crucial for proper physiological functions, undergoes changes with aging, and is disturbed in several neurological disorders. In this review, we analyze the impact of disruption in this equilibrium on physiological aging and the onset of pathological conditions. Alzheimer´s disease (AD) is a multifactorial neurodegenerative disorder in the elderly, characterized by the increased presence of the Aβ peptide, which supports the amyloid hypothesis of the disease. However, AD also involves a progressive loss of cholinergic innervation, leading to the cholinergic hypothesis of the disease. Nicotinic acetylcholine receptors (nAChRs) are transmembrane proteins, and Aβ peptides, their oligomeric and fibrillar species, which increase in hydrophobicity as they develop, interact with membranes. Therefore, a membrane hypothesis of the disease emerges as a bridge between the other two. Here, we discuss the impact of the membrane environment, through direct or indirect mechanisms, on cholinergic signaling and Aβ formation and subsequent incorporation into the membrane, with a special focus on the crucial role of cholesterol in these processes.

生物膜是由各种分子组成的复杂实体，具有横向和跨双分子层脂质不对称性，以及不同膜蛋白的选择性空间分布。这种动态的协调对正常的生理功能至关重要，随着年龄的增长而发生变化，并在一些神经系统疾病中受到干扰。在这篇综述中，我们分析了这种平衡的破坏对生理衰老和病理条件发作的影响。阿尔茨海默病（AD）是一种多因素的老年人神经退行性疾病，其特征是a β肽的存在增加，这支持了该疾病的淀粉样蛋白假说。然而，阿尔茨海默病也涉及胆碱能神经支配的进行性丧失，导致疾病的胆碱能假说。烟碱乙酰胆碱受体（nAChRs）是跨膜蛋白和Aβ肽，它们的寡聚体和纤维状物种，随着它们的发育，疏水性增加，与膜相互作用。因此，该疾病的膜假说成为其他两种假说之间的桥梁。在这里，我们讨论了膜环境的影响，通过直接或间接的机制，对胆碱能信号和a β的形成和随后并入膜，特别关注胆固醇在这些过程中的关键作用。

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引用次数: 0

Membranes, where lipids and protein meet 细胞膜是脂质和蛋白质相遇的地方

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids

Pub Date : 2025-03-22 DOI: 10.1016/j.chemphyslip.2025.105486

Diego de Mendoza

Membrane proteins have central roles in a vast number of vital cellular processes. A common structural feature of most membrane proteins is the presence of one or more hydrophobic alpha-helices that interact with the lipid bilayer. Because of the interaction with the surrounding lipids, the organization of these helices will be sensitive to lipid properties like fluidity and hydrophobic thickness. The helices may adapt to the lipids in different ways, which in turn can influence the structure and function of the intact membrane protein. In this review article, I will focus on how the lipid environment governs the signaling state of a transmembrane protein and in how the lipid bilayer influences the catalytic and substrate channeling role of a peripheral protein.

膜蛋白在大量重要的细胞过程中发挥着核心作用。大多数膜蛋白的共同结构特征是存在一个或多个与脂质双分子层相互作用的疏水α-螺旋。由于与周围脂质的相互作用，这些螺旋的组织结构会对脂质特性（如流动性和疏水性厚度）很敏感。螺旋可能会以不同的方式适应脂质，进而影响完整膜蛋白的结构和功能。在这篇综述文章中，我将重点讨论脂质环境如何支配跨膜蛋白的信号状态，以及脂质双分子层如何影响外周蛋白的催化和底物通道作用。

引用次数: 0

The reverse sequence of Aβ amyloid self-triggers isolated nano-fibers and oligomers in lipid environment 在脂质环境中，Aβ淀粉样蛋白的反向序列自触发分离纳米纤维和低聚物。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids

Pub Date : 2025-03-21 DOI: 10.1016/j.chemphyslip.2025.105485

Alain Bolaño Alvarez , María Elisa Mariani , Pablo E.A. Rodríguez , Gerardo D. Fidelio

Nanostructured lipid/peptide film at air/water interface allow to build different molecular arrangements depending of peptide sequence, peptide proportion and type of lipid. We studied the surface properties of Aβ(1 −42) and its retro-isomer Aβ(42 −1) amyloid peptides mixed with 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) lipid at the air/water interface. In absence of lipids, pure form of both Aβ(1 −42) and Aβ(42 −1) form insoluble monolayer films without appreciable fibril-like structures despite the high interfacial confinement. We show the lipid/peptide interfacial organization depends on the reversing sequence peptide in lipid enriched environment. In POPC/Aβ(1 −42) mixed film we have observed network fibril-like structures. However, using Aβ(42 −1) retro-isomer peptide to form the mixed film, the induced structuration acquired an isolated fibers arrangement associated with oligomers. The above structures are clearly visualized at the interface by using Brewster Angle Microscopy. In the same way, the isolate fibers and oligomers become Thioflavin T positive when they are observed by Fluorescence Microscopy. Thus, we attributed an amyloid behavior at the air/water interface that was also evidenced by Scanning Electron Microscopy when the mixed film was transferred to mica support. Changes from an exclusive β-sheet in pure peptide to a notable increase in α-helix/unordered conformations were induced by the presence of the lipid keeping with fibril-like structures. We postulated that the amyloid fibril formation at the membrane interface not only depends on the interfacial lipid environment and the low amyloid peptide content but also by the reversing sequencing that imposed a differential lipid/peptide interaction at the interface. Despite the retro-isomer peptide has not impact nor the overall molecular hydrophobicity neither on the interfacial behavior although perform a “conformational selective process” that depends on the β-sheet and α-helix contents.

空气/水界面的纳米脂质/肽膜允许根据肽序列、肽比例和脂质类型构建不同的分子排列。我们研究了Aβ(1-42)及其反转录异构体Aβ(42-1)淀粉样肽与1-棕榈酰-2-油酰-磷脂酰胆碱（POPC）脂混合在空气/水界面上的表面性质。在没有脂质的情况下，纯形式的Aβ(1-42)和Aβ(42-1)形成不溶性单层膜，尽管界面约束高，但没有明显的纤维样结构。我们发现脂质/肽的界面组织依赖于脂质富集环境中肽的反转序列。在POPC/Aβ(1-42)混合膜中，我们观察到网状纤维样结构。然而，使用Aβ(42-1)逆转录异构体肽形成混合膜，诱导的结构获得了与低聚物相关的孤立纤维排列。使用布鲁斯特角度显微镜，上述结构在界面上清晰可见。以同样的方式，分离纤维和低聚物在荧光显微镜下观察时呈硫黄素T阳性。因此，当混合膜转移到云母载体上时，我们归因于空气/水界面的淀粉样蛋白行为，扫描电子显微镜也证实了这一点。由纯肽的专属β-片转变为α-螺旋/无序构象的显著增加，是由具有纤维样结构的脂质保持的存在引起的。我们假设，膜界面淀粉样纤维的形成不仅取决于界面脂质环境和低淀粉样肽含量，还取决于在界面上施加差异脂质/肽相互作用的反向测序。尽管逆转录异构体肽对分子整体疏水性和界面行为没有影响，但它的“构象选择过程”取决于β-片和α-螺旋的含量。

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引用次数: 0

Corrigendum to: “Nanodisc assembly from bacterial total lipid extracts” [Chem. Phys. Lipids (2024) 105425] “细菌总脂质提取物的纳米圆盘组装”的更正[化学]。理论物理。脂类（2024）105425]。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids

Pub Date : 2025-02-18 DOI: 10.1016/j.chemphyslip.2025.105476

Trent R. Llewellyn, Olivia R.C. Pimentel, Kiersten D. Lenz, Makaela M. Montoya, Jessica Z. Kubicek-Sutherland

引用次数: 0

Bending the rules: Molecular dynamics of hydroxylated sphingolipid membranes with 2-hydroxyoleic acid 弯曲规则：2-羟基油酸羟基化鞘脂膜的分子动力学。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids

Pub Date : 2025-02-11 DOI: 10.1016/j.chemphyslip.2025.105475

Lucia Sessa , Simona Concilio , Miriam Di Martino , Davide Romanini , Xavier Busquets , Stefano Piotto

In this study, we introduce a novel method for quantifying the mechanical properties of lipid membranes-bending rigidity (κ), Gaussian rigidity (κ_G), and surface tension (γ) using molecular dynamics (MD) simulations. Our approach is applied to membranes incorporating 2-hydroxyoleic acid (2OHOA), a synthetic oleic acid derivative currently under clinical investigation for its anticancer properties. 2OHOA modifies the plasma membrane composition in cancer cells and activates sphingomyelin synthase 1 (SMS1), an enzyme critical for maintaining sphingolipid levels in the plasma membrane. This research focuses on how the integration of 2OHOA into ceramide and sphingomyelin alters the mechanical and biophysical properties of these membranes. We employed MD simulations to analyze structural parameters such as lipid area, volume, and bilayer thickness. Additionally, by constructing a system of linear equations based on the Helfrich-Seifert model, we estimated the mechanical properties of hydroxylated versus non-hydroxylated membranes. Our findings reveal significant membrane rigidity and curvature changes due to hydroxylation, affecting membrane-protein interactions and cellular processes like vesiculation. This work provides critical insights into the molecular mechanisms by which hydroxylation influences membrane elasticity, with implications for both fundamental biophysics and therapeutic applications in cancer treatment.

在这项研究中，我们引入了一种新的方法来量化脂质膜的力学性能-弯曲刚度（κ），高斯刚度（κ g）和表面张力（γ）使用分子动力学（MD）模拟。我们的方法被应用于含有2-羟基油酸（2OHOA）的膜，这是一种合成油酸衍生物，目前正在临床研究其抗癌特性。2OHOA改变癌细胞的质膜组成，激活鞘磷脂合成酶1 (SMS1)，这是维持质膜鞘脂水平的关键酶。本研究的重点是将2OHOA整合到神经酰胺和鞘磷脂中，如何改变这些膜的力学和生物物理特性。我们使用MD模拟来分析结构参数，如脂质面积、体积和双层厚度。此外，通过构建基于hellich - seifert模型的线性方程组，我们估计了羟基化膜与非羟基化膜的力学性能。我们的研究结果表明，由于羟基化作用，膜刚度和曲率发生了显著变化，影响了膜-蛋白相互作用和细胞过程，如泡化。这项工作为羟基化影响膜弹性的分子机制提供了重要的见解，对基础生物物理学和癌症治疗中的治疗应用都有意义。

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引用次数: 0

Combined impact of pesticides on mono- and bilayer lipid membranes 农药对单层和双层脂质膜的综合影响。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids

Pub Date : 2025-02-03 DOI: 10.1016/j.chemphyslip.2025.105474

Luis Fernando do Carmo Morato , Gilia Cristine Marques Ruiz , Carlos Junior Amorim Lessa , Danilo da Silva Olivier , Marcos Serrou do Amaral , Orisson Ponce Gomes , Wallance Moreira Pazin , Augusto Batagin-Neto , Osvaldo N. Oliveira Jr , Carlos José Leopoldo Constantino

The increased use of agrochemicals in crop production raises concerns about the risk of combined pesticide exposure through water and food, potentially leading to a ‘cocktail effect’ with synergistic impacts on human health. To investigate such effects, we used the pesticides acephate and diuron interacting with a mimetic system of the cell membrane, composed of lipid monolayers. These mimetic systems were composed by a mixture of POPC, cholesterol and sphingomyelin (70/20/10 mol%), respectively, close to the composition found in mammalian membranes. Results from Langmuir monolayers, including surface pressure-area isotherms, polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), and Brewster angle microscopy (BAM), showed that the pesticides interact predominantly with the polar head region of the lipids, a finding supported by density functional theory (DFT) calculations and molecular dynamics simulations. The cocktail had a similar effect in π-A isotherms; however, PM-IRRAS data suggests a stronger effect of the cocktail on the ternary monolayer at the molecular level, once the pesticide mixture changed the conformation and orientation of the headgroup and disturbed the hydrocarbon chain. These results evidence the impact of the ‘cocktail effect’ on lipid membranes, highlighting potential health risks associated with pesticide mixtures.

农用化学品在作物生产中使用的增加引起了人们对通过水和食物接触混合农药的风险的关注，这可能导致对人类健康产生协同影响的“鸡尾酒效应”。为了研究这种影响，我们使用杀虫剂甲胺磷和迪乌隆与细胞膜的模拟系统相互作用，由脂质单层组成。这些模拟系统分别由POPC、胆固醇和鞘磷脂（70/20/10mol %）的混合物组成，接近于哺乳动物膜中的成分。Langmuir单层膜的表面压力-面积等温线、偏振调制红外反射吸收光谱（PM-IRRAS）和Brewster角度显微镜（BAM）的结果表明，农药主要与脂质的极性头区相互作用，这一发现得到了密度泛函数理论（DFT）计算和分子动力学模拟的支持。鸡尾酒在π-A等温线上也有类似的效果；然而，PM-IRRAS数据表明，在分子水平上，一旦农药混合物改变了头基的构象和取向并扰乱了烃链，鸡尾酒对三元单层的影响就会更强。这些结果证明了“鸡尾酒效应”对脂质膜的影响，突出了与农药混合物相关的潜在健康风险。

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引用次数: 0

Interaction of biomimetic lipid membranes with detergents with different physicochemical characteristics 仿生脂膜与不同理化性质洗涤剂的相互作用。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids

Pub Date : 2025-02-01 DOI: 10.1016/j.chemphyslip.2025.105473

Mariana S.S. Oliveira, Amanda C. Caritá, Karin A. Riske

Membrane solubilization by detergents is routinely performed to separate membrane components, and to extract and purify membrane proteins. This process depends both on the characteristics of the detergent and properties of the membrane. Here we investigate the interaction of eight detergents with very distinct physicochemical features with model membranes in different biologically relevant phases. The detergents chosen were the non-ionic Triton X-100, Triton X-165, C10E5, octyl glucopyranoside (OG) and dodecyl maltoside (DDM) and the ionic sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium bromide (CTAB) and Chaps. Three lipid compositions were explored: pure palmitoyl oleoyl phosphatidylcholine (POPC), in the liquid-disordered (Ld) phase, sphingomyelin (SM)/cholesterol 7:3 (chol) in the liquid-ordered (Lo) phase and the biomimetic POPC/SM/chol 2:1:2, which might exhibit Lo/Ld phase separation. Turbidity measurements of small liposomes were performed along the titration with the detergents to obtain the overall solubilization profiles and optical microscopy of giant unilamellar vesicles (GUVs) was used to reveal the mechanism of interaction of the detergents. The presence of cholesterol renders the membranes partly/fully insoluble in all detergents, and the charged detergents are the least effective to solubilize POPC. The non-ionic detergents, with exception of DDM, with the bulkiest headgroup, caused a substantial increase in surface area of POPC, which was quantified directly on single GUVs. The other detergents induced mainly vesicle burst. Detergents that caused some increase in area induced Lo/Ld phase separation in the ternary mixture, with preferential solubilization of the latter. The insoluble area fraction left intact was quantified. Overall, the non-ionic detergents were the most effective in solubilizing lipid membranes.

通常使用洗涤剂对膜进行增溶，以分离膜组分，提取和纯化膜蛋白。这一过程取决于洗涤剂的特性和膜的性能。在这里，我们研究了八种具有不同物理化学特征的洗涤剂与不同生物相关相的模型膜的相互作用。选用非离子型Triton X-100、Triton X-165、C10E5、辛基葡萄糖苷（OG）和十二烷基麦芽糖苷（DDM）以及离子型十二烷基硫酸钠（SDS）、十六烷基三甲基溴化铵（CTAB）和Chaps。研究了三种脂质组成：液体无序相（Ld）中纯棕榈酰油酰磷脂酰胆碱（POPC），液体有序相（Lo）中鞘磷脂(SM)/胆固醇7:3 (chol)，以及可能表现Lo/Ld相分离的仿生POPC/SM/chol 2:1:2。在滴定过程中，通过测量小脂质体的浊度来获得洗涤剂的整体增溶情况，并通过光学显微镜观察巨型单层囊泡（GUVs）来揭示洗涤剂相互作用的机制。胆固醇的存在使膜部分/完全不溶于所有洗涤剂，而带电洗涤剂对POPC的溶解效果最差。除DDM外，头基最大的非离子型洗涤剂使POPC的表面积显著增加，这是在单个guv上直接量化的。其他洗涤剂主要引起囊泡破裂。导致面积增加的洗涤剂会导致三元混合物中Lo/Ld相分离，后者优先增溶。对不溶性面积分数进行定量分析。总的来说，非离子洗涤剂在溶解脂质膜方面是最有效的。

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引用次数: 0

Broad-based targeted lipidomic analysis of dental fluorosis population in an adult population 成人氟牙症人群的基础广泛靶向脂质组学分析。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids

Pub Date : 2025-01-09 DOI: 10.1016/j.chemphyslip.2025.105471

Huiying Kong , Shanshan Liu , Zhenzhen Li , Li Xu , Kai Zhang , Yuanyin Wang

Dental fluorosis, as a common chronic fluoride toxicity oral disease, is mainly caused by long-term excessive intake of fluoride, which seriously affects the aesthetics and function of patients' teeth. In recent years, with the rapid development of metabolomics technology, lipidomics, as an important means to study the changes in lipid metabolism in organisms, has shown great potential in revealing the mechanisms of disease development. As a major component of cell membranes and a signaling molecule, metabolic disorders of lipids are closely related to a variety of diseases, but the specific mechanism of action in dental fluorosis is still unclear. Therefore, the present study aimed to systematically analyze the differences in lipid profiles between dental fluorosis patients and healthy populations by using broad-based targeted lipidomics technology to provide new perspectives on the pathogenesis of dental fluorosis. To this end, the researchers compared the salivary lipidome of healthy participants with the salivary micro lipidome of dental fluorosis patients. Their saliva samples were collected, and advanced broad-based targeted lipidomics technology, combined with a high-performance liquid chromatography-mass spectrometry (LC-MS) system, was used to comprehensively detect and quantify the lipids in the samples. The lipid data were processed and analyzed by bioinformatics to identify the unique patterns of changes in the lipid profiles of dental fluorosis patients and to verify the significance of these changes using statistical methods. Several glycerophospholipids, fatty acyls, and sphingolipids exhibited marked alterations in dental Among these, glycocholic acid, LPA (18:4), taurolithocholic acid-3-sulfate, lithocholic acid-3-sulfate, and taurochenodeoxycholic acid-3-sulfate were observed between dental fluorosis patients and healthy controls. taurochenodeoxycholic acid was significantly decreased, while PA (12:0_12:0) levels were significantly elevated. These findings suggest that These findings suggest that disturbances in lipid metabolism play a crucial role in developing dental fluorosis.

氟斑牙是一种常见的慢性氟毒性口腔疾病，主要是由于长期过量摄入氟化物，严重影响患者牙齿美观和功能所致。近年来，随着代谢组学技术的迅速发展，脂质组学作为研究生物体内脂质代谢变化的重要手段，在揭示疾病发生机制方面显示出巨大的潜力。脂质作为细胞膜的主要成分和信号分子，代谢紊乱与多种疾病密切相关，但在氟斑牙中的具体作用机制尚不清楚。因此，本研究旨在通过广泛的靶向脂质组学技术，系统分析氟牙症患者与健康人群的脂质谱差异，为氟牙症的发病机制提供新的视角。为此，研究人员将健康参与者的唾液脂质组与氟斑牙患者的唾液微脂质组进行了比较。采集唾液样本，采用先进的基础广泛的靶向脂质组学技术，结合高效液相色谱-质谱（LC-MS）系统，对样本中的脂质进行全面检测和定量。对脂质数据进行生物信息学处理和分析，以确定氟牙症患者脂质谱变化的独特模式，并使用统计学方法验证这些变化的意义。几种甘油磷脂、脂肪酰基和鞘脂在牙齿中表现出明显的变化，其中，糖胆酸、LPA（18:4）、牛磺酸-3-硫酸石胆酸、硫酸石胆酸-3-硫酸石胆酸和牛磺酸-3-硫酸去氧胆酸在氟斑牙患者和健康对照组中被观察到。taurochenodeoxycholic acid显著降低，PA（12:0 ~ 12:0）水平显著升高。这些发现表明脂质代谢紊乱在氟斑牙的发生中起着至关重要的作用。

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引用次数: 0

Electrophysiological dissection of the ion channel activity of the Pseudomonas aeruginosa ionophore protein toxin Tse5 铜绿假单胞菌离子载体蛋白毒素Tse5离子通道活性的电生理解剖。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids

Pub Date : 2025-01-06 DOI: 10.1016/j.chemphyslip.2025.105472

Jessica Rojas-Palomino , Jon Altuna-Alvarez , Amaia González-Magaña , María Queralt-Martín , David Albesa-Jové , Antonio Alcaraz

We present an in-depth electrophysiological analysis of Tse5, a pore-forming toxin (PFT) delivered by the type VI secretion system (T6SS) of Pseudomonas aeruginosa. The T6SS is a sophisticated bacterial secretion system that injects toxic effector proteins into competing bacteria or host cells, providing a competitive advantage by disabling other microbes and modulating their environment. Our findings highlight the dependency of Tse5 insertion on membrane charge and electrolyte concentration, suggesting an in vivo effect from the periplasmic space. Conductance and selectivity experiments reveal a predominant and reproducible pore architecture of Tse5, characterized by a weak cation selectivity without chemical specificity. pH titration experiments suggest a proteolipidic pore structure influenced by both protein and lipid charges, a hypothesis further supported by experiments involving engineered mutants of Tse5 with altered glycine zippers. These results significantly advance our understanding of Tse5's molecular mechanism of toxicity, paving the way for potential applications in biosensing and macromolecular delivery.

本文对铜绿假单胞菌（Pseudomonas aeruginosa） VI型分泌系统（T6SS）释放的成孔毒素（PFT） Tse5进行了深入的电生理分析。T6SS是一种复杂的细菌分泌系统，它将有毒效应蛋白注射到竞争细菌或宿主细胞中，通过使其他微生物丧失功能并调节其环境来提供竞争优势。我们的研究结果强调了Tse5的插入对膜电荷和电解质浓度的依赖性，这表明在体内有来自质周空间的影响。电导和选择性实验揭示了Tse5的主要和可复制的孔隙结构，其特征是弱阳离子选择性，没有化学特异性。pH滴定实验表明，蛋白脂质孔隙结构受到蛋白和脂质电荷的影响，这一假设进一步得到了具有改变甘氨酸拉链的工程突变体Tse5的实验的支持。这些结果极大地促进了我们对Tse5毒性分子机制的理解，为其在生物传感和大分子传递方面的潜在应用铺平了道路。

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引用次数: 0