Trans-Resveratrol Decreases Membrane Water Permeability: A Study of Cholesterol-Dependent Interactions
Trans-Resveratrol Decreases Membrane Water Permeability: A Study of Cholesterol-Dependent Interactions
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DOI：
10.1007/s00232-022-00250-0
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发表时间：
2022-06-24
影响因子：
2.4
通讯作者：
Lee, Sunghee
中科院分区：
文献类型：
--
作者：
Ceja-Vega, Jasmin;Perez, Escarlin;Lee, Sunghee
白藜芦醇（Resveratrol，RSV）是一种具有生物活性的植物酚，由于其能够调节影响细胞生长和转移的细胞内靶点和信号通路，已被广泛研究用于癌症预防和治疗。RSV和细胞膜之间的非特异性相互作用可以调节膜的物理性质，这反过来又可以影响蛋白质的构象并扰乱膜宿主的生物学功能。本研究考察了RSV与具有不同浓度胆固醇（Chol）的模型膜的非特异性相互作用，模拟正常和癌细胞。通过使用液滴界面双层（DIB）模型、来自差示扫描量热法的向热性质和来自共焦拉曼光谱的结构性质的水渗透性参数的变化来感测RSV对模型膜的扰动，所有这些都是通过使用本身可能扰动膜的探针而不复杂的技术。相互作用的性质和程度在很大程度上取决于Chol的存在和不存在以及RSV的浓度。我们的研究结果表明，RSV的存在下，由1，2-二油酰基-sn-甘油-3-磷酸胆碱（DOPC），表明RSV的能力，在硬化流体膜的脂质膜的水渗透性降低。然而，当存在Chol时（DOPC与胆固醇的摩尔比为4：1和2：1），RSV的加入对水渗透性没有显著影响。DSC热谱图显示RSV与DOPC和DOPC/Chol双层相互作用，并以浓度依赖性方式影响其热致相行为，通过降低主要相变温度和焓，在较高浓度的RSV下显示相分离。拉曼光谱研究表明RSV对DOPC支撑的双层的有序化效应，在Chol存在下有序化程度较低。这些研究的综合结果分别突出了RSV对无Chol和富含Chol的膜的不同作用，这些结果构成了增加白藜芦醇在疾病治疗（包括癌症）中的理解和有效使用的领头羊。[图形]。
Resveratrol (RSV), a biologically active plant phenol, has been extensively investigated for cancer prevention and treatment due to its ability to regulate intracellular targets and signaling pathways which affect cell growth and metastasis. The nonspecific interactions between RSV and cell membranes can modulate physical properties of membranes, which in turn can affect the conformation of proteins and perturb membrane-hosted biological functions. This study examines non-specific interactions of RSV with model membranes having varying concentrations of cholesterol (Chol), mimicking normal and cancerous cells. The perturbation of the model membrane by RSV is sensed by changes in water permeability parameters, using Droplet Interface Bilayer (DIB) models, thermotropic properties from Differential Scanning Calorimetry, and structural properties from confocal Raman spectroscopy, all of which are techniques not complicated by the use of probes which may themselves perturb the membrane. The nature and extent of interactions greatly depend on the presence and absence of Chol as well as the concentration of RSV. Our results indicate that the presence of RSV decreases water permeability of lipid membranes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), indicating a capability for RSV in stiffening fluidic membranes. When Chol is present, however, (at 4:1 and 2:1 mol ratio DOPC to cholesterol), the addition of RSV has no significant effect upon the water permeability. DSC thermograms show that RSV interacts with DOPC and DOPC/Chol bilayers and influences their thermotropic phase behavior in a concentration-dependent manner, by decreasing the main phase transition temperature and enthalpy, with a phase separation shown at the higher concentrations of RSV. Raman spectroscopic studies indicate an ordering effect of RSV on DOPC supported bilayer, with a lesser extent of ordering in the presence of Chol. Combined results from these investigations highlight a differential effect of RSV on Chol-free and Chol-enriched membranes, respectively, which results constitute a bellwether for increased understanding and effective use of resveratrol in disease therapy including cancer.[GRAPHICS].