Effects of cell membrane phospholipid level and protein kinase C isoenzyme expression on hepatic metastasis of colorectal carcinoma

BACKGROUND: The molecular mechanism of hepaticmetastasis of colorectal cancer is not well understood. Theaim of this study was to assess the relations between phos-pholipid contents of cellular membrane and isoenzyme ex-pression of protein kinase C (PKC) and their effects on he-patic metastasis of colorectal cancer.METHODS: High performance liquid chromatography wasused to detect contents of cell membrane phospholipids:phosphatidylinosital (PI), phosphatidylserine (PS), phos-phatidylethanolamine (PE) and phosphatidylcholine (PC)in primary foci, paratumor mucosa and hepatic metastaticfoci in patients with colorectal carcinoma. The mRNA ex-pression levels of PKC-α, -δ, -ε, -λ, -ξ isoenzymeswere detected with the QRT-PCR technique.RESULTS: The levels of PI, PC and PE in primary foci andhepatic metastatic foci were higher than those in paratumormucosa. The level of PE in hepatic metastatic foci wasmuch higher than that in primary foci (t =98.88, P <0.01);but the levels of PI and PC were not significantly differentbetween primary foci and hepatic metastatic foci (t =1.73 ,1.36, P>0.05). The expression levels of -δ, -ε,-λ, -ξ were enhanced in primary foci and hepatic metasta-tic foci, but the level of PKC-α in primary foci was de-creased as compared with that in paratumor mucosa. Thelevels of PKC-δ, -ε, -λ, -ξ in hepatic metastatic foci werehigher than those in primary foci. A positive correlationwas observed between the expression levels of PI, PC andand also between those of PE and PKC-δ, -ε, -λ,-ξ. However, there was a close negative correlation be-tween PE and PKC-α.CONCLUSION: Increased levels of PI and PC and de-creased ratio of PKC-α to are related to colorectalcancer genesis. Increased levels of PE, increased expressionof PKC-δ, -ε, -λ, -ξ isoenzymes and decreased level ofPKC-α are related to hepatic metastasis in colorectal carci-noma.

Hexagonal arrangement of phospholipids in bilayer membranes

The phospholipid membrane plays a key role in myriad biological processes and phenomena, and the arrangement structure of membrane determines its function. However, the molecular arrangement structure of phospholipids in cell membranes is difficult to detect experimentally. On the basis of molecular dynamic simulations both in a non-destructive way and at native environment, we observed and confirmed that the phospholipids self-assemble to a hexagonal arrangement structure under physiological conditions. The underlying mechanism was revealed to be that there are hexagonal arrangement regions with a lower free energy around each lipid molecule. The findings potentially advance the understanding of biological functions of phospholipid bilayers.

SUPPRESSION OF CELL ADHESION ON POLYACRYLONITRILE-BASED MEMBRANES BY THE ANCHORING OF PHOSPHOLIPID MOIETIES

In this work, the membrane surface of poly（acrylonitrile-co-2-hydroxyethyl methacrylate） （PANCHEMA） was chemically modified by anchoring of phospholipid moieties. The process involved the reaction of hydroxyl groups on the membrane surface with 2-chloro-2-oxo-1,3,2-dioxaphospholane （COP） followed by the ring-opening reaction of COP with trimethylamine. Chemical differences between the original and the modified membranes were characterized by FT-IR and XPS, It was found that the amount of macrophage adhered on the modified membrane surface is substantially lower than that on polyacrylonitrile （PAN） and PANCHEMA membranes under the same condition, The morphological change of the adherent cell is also suppressed by the generation ofphospholipid moieties on the membrane surface.

Study on Phospholipid Composition of Erythrocyte Membrane in Hypophosphatemic Cows

The phospholipid constituents of the erythrocyte membrane of cows in hypophosophorus were detected with the field cases and the group comparison. The cows were divided into three groups: the hemoglobinuria group (HN), the hypophosphatemia group (HP) and the control group (CK). The content of the phospholipid constituent in HN and HP obviously changed: phosphatidylethaanolamine (PE) content in HN was significantly lower than that in HP and CK; but sphingomyline (SM) and phosphatidycholine (PC) + phosphatidylserine (PS) content in HN were significantly higher than that in the two other groups; in comparison between HP and CK, PC + PS content was lower and SM content was higher in HP; significant positive correlation and negative correlation were observed between serum phosphorus and PE content, serum phosphorus and SM content respectively.

Effects of Dietary Phospholipids on Na^+-K^+-ATPase Activity and Cell Membrane Fatty Acid Composition in Gill of Catfish (Pangasius sutchi)

[ Objective] The aim of this study was to determine the effects of dietary phospholipids on Na＋ - K＋ - ATPase activity and cell mem- brane fatty acid composition in the gill of catfish （Pangasius sutchi）. [Method] 900 healthy catfish （1.4 ±0.08 g of average weight） were randomly divided into five groups. Dietary phospholipids level of group PL0 was 0%, and 1%, 2%, 3%, 4% for group PL1, PL2, PL3, PL4, respectively. The experiment lasted for 56 days. [Result] The results showed that the Na＋ -K＋ -ATPase activity in gill decreased gradually with the increase of the dietary phospholipids level （ P 〈0.05）. Cell membrane fatty acid composition was affected significantly by dietary phospholipids. The content of saturated fatty acids and monounsaturated fatty acids of group PLO was the highest （ P 〈 0.05）, however, it had the lowest content of highlyunsatu- rated fatty acids （ P 〈 0.05）. The content of polyunsaturated fatty acids of group 3 was higher than group 0 and group 1 （ P 〈 0.05）. E Conclusion] The results indicated that there is obvious compensation effects on Na＋ -K＋ -ATPase activity with phospholipids content changes in gills of catfish （ Pangasius sutchi） to maintain stable physiological level and normal basal metabolism and the increase of HUFA and ∑PUFA is necessary for gill cell membrane to better maintain and perform normal physiological function.

PROTECTIVE EFFECTS OF CAPTOPRIL AND COENZYME Q10 ON THE MITOCHONDRIAL MEMBRANE－PHOSPHOLIPID INJURY OF LYMPHOCYTES IN PATIENTS

The membrane-phospholipid (MPL)injury of myocardial cells may play an important role in the development of heart failure.In present study, peripheral lymphocytes were used as a study model in which the protective and reparative effects of Captopril and Cocnzyme 10 (Coo10)on mitochondrial MPL injury were observed. 42 hospitalized patients with dilated cardiomyopathy(DCM),on conventional anti-heart-failure therapy, were divided into three groups at random,and Captopil (Capton),Neuquinone 10 (CoQ10) and placebo were added respectively.The A4PL localization was proceeded by modified Demer's tricomplex flocculation.After mean 75'5 days observation,in Captopril and CoQ10 groups, heart function was improved,with circulatory A1 decreased,the degree of mitochondrial proliferation of lymphocytes decreased and the mitochondrial MPL injury repaired in certain degree.The percentages of the lymphocytes with less than 5 mitochondria per lymphocyte increased [(60.0± 9.4)vs (72.0± 6. 8)% for Captopril;(55.0±8.9) vs (73.1 ± 9. 8)% for CoQ10, P<0. 001];the percentages of mitochondria with intact MPL localization increased [(59. 1 ± 8. 1 ) vs (72. 0± 9. 4)% for Captopril;(56.6±9.3) vs (73.8±9. 4)% for CoQ10 P< 0.001].But no significant changes were found in either the proliferation or MPL injury in the con trols. In conclusion,Captopril and CoQ10 have a beneficial effects on the protection and reparation of mitochondrial injury in patients with DCM.

Formation mechanism for stable system of nanoparticle/protein corona and phospholipid membrane

In the physiological environment, nanoparticles(NPs) interact with proteins to form a protein-rich layer on the surface which is called "protein corona". Understanding and analyzing the formation process of protein corona and protein corona-nanoparticles is of great significance for biological related nano research. Many separation techniques have been used to analyze the composition of protein corona, but in situ analysis of protein corona is still absent. With the development of detection technology, sum frequency generation(SFG) is an effective instrument to analyze the surface protein structure and dynamic changes of protein corona in situ. In this work the molecular mechanism and surface structure effect of the interaction between nanoparticles with surface protein corona(S-NPP) and phospholipid membrane were studied. When S-NPP interacts with phospholipid membrane, the bond affinity network formed by the binding water can stabilize S-NPP around the lipid bilayer. In this process, S-NPP can be found wrapped in the hydration shell. This ultimately leads to a more moderate interaction between particles and phospholipid membrane.

Membrane Lipid Replacement: Clinical Studies Using a Natural Medicine Approach to Restoring Membrane Function and Improving Health

Functional oral supplements containing cell membrane glycerolphospholipids and antioxidants have been used to safely replace damaged membrane lipids that accumulate during aging and in various clinical conditions. This approach differs from other dietary and intravenous interventions in the composition of phospholipids and the presence of fructooligosaccharides that protect the phospholipids against oxidation and bile and enzymatic damage. Various chronic clinical conditions are characterized by membrane phospholipid oxidative damage, resulting in loss of cellular function. Recent clinical trials have shown the benefits of Membrane Lipid Replacement in replenishing damaged membrane lipids and restoring mitochondrial function, resulting in reductions in fatigue in aged subjects and patients with a variety of clinical diagnoses. Recent in vitro experiments with nonphysiological concentrations of phospholipids did not result in enhancement of mitochondrial electron transport enzyme activities. This can be explained by the use of the wrong phospholipid fatty acids, over-dilution of membrane constituents and mitochondrial swelling. A similar phenomenon was seen when human sperm were incubated in vitro with high concentrations of glycerolphospholipids and their motility was assessed. Only lower, more physiological concentrations of glycerolphospholipids stimulated sperm motility. Additional studies are needed to determine the functional effects of Membrane Lipid Replacement on other cellular membranes, such as the plasma membrane and other intracellular membranes of various cells and tissues.

Changes of pulmonary beta-adrenergic receptors and their relationship with membranous phospholipid metabolism in endotoxin-induced lung injury in rats

The changes of beta-adrenergic receptors (AARs) in lung tissue in endotoxin-induced acute lung injury was investigated with radioligand bindig assay in rats. The lipid fluidity and phospholipid content of the cellular membrane of lung tissue were measured with fluorescent polarization and high performance liquid chromatography respectively. The findings were as follows:1- Four hours after endotoxin injection, there was a 47% decrease of the maximal binding capacity of fyARsas compared with the control.2. Endotoxin was able to decrease the lipid fluidity and phospholipid content of the pulmonary cellular membrane markedly and at the same time. There was an elevated activity of phospholipase A2 in the pulmonary tissueThese findings suggest that the decrease of the binding capacity of &ARs results in a decrease of the PAR mediated functions, which plays a ro1e in the pathogensis of endotoxin-induced acute lung injury and the activation of phospholipase A2 which is an important factor to reduce the phospholipid content of cell membrane and subsequently to decrease its lipid fluidity, can result in a reduction of the lateral diffusion and rotatory movement of β-ARs and to decrease the chances of β-ARs to bind with the ligands.

水稻OsMGD2和OsMGD3基因的功能鉴定及其对烟草耐低磷胁迫的影响

【目的】单半乳糖甘油二酯合酶(MGD)是合成单半乳糖甘油二酯(MGDG)的关键酶,在植物响应低磷胁迫过程中起着重要作用。为系统了解水稻OsMGD2和OsMGD3基因在低磷胁迫响应中的作用和功能。【方法】用盆栽试验分析正常和低磷条件下野生型(SR1)、过表达OsMGD2和OsMGD3转基因烟草的生理响应及脂质组分的变化。【结果】无论在正常还是低磷条件下,转基因与野生型烟草的磷含量无显著差异,但转基因烟草的生物量、叶绿素含量和光合能力均显著高于野生型。转基因烟草在低磷胁迫下的磷脂(PL)含量、双半乳糖甘油二酯(DGDG)含量、DGDG与MGDG的比值和半乳糖脂(GL)与PL的比值均显著高于野生型烟草,且OsMGD3转基因烟草的脂质含量和比值均高于OsMGD2转基因烟草。【结论】通过调控水稻OsMGD2/3基因表达,可提高植物低磷下的膜脂重塑能力,进而维持植物在低磷胁迫下较高的光合和生长能力,增加植物的低磷耐受性。

五种树坚果油体的结构组成与稳定性

【目的】在油料种子中,脂类物质主要以油体的形式存在。核桃、榛子等树坚果是重要的木本油料,通过比较5种树坚果油体在形态、组成和稳定性上的差异,同时探讨三者间的关系,为木本坚果油脂的利用提供新途径。【方法】以核桃、巴旦木、榛子、薄壳山核桃、松子5种树坚果为研究对象,利用透射电镜对种仁细胞内油体的形态和大小进行观察比较;采用SDS-PAGE技术对油体膜蛋白进行分离,切取蛋白条带进行LC-MS/MS质谱鉴定;利用脂质组学对油体膜磷脂和油体内部甘油三酯组成进行分析;基于室温储藏条件下油体的形态变化,结合测定过氧化值和硫代巴比妥酸值,对油体稳定性进行评价。【结果】5种树坚果种仁细胞内均充斥油体和蛋白体,油体具完整包膜,形态多呈非对称椭球形,最大平均粒径为薄壳山核桃油体(2.34±0.48)μm,最小为巴旦木油体(1.21±0.19)μm。油质蛋白(oleosin)是5种树坚果最主要的油体膜蛋白组分,占膜蛋白总量的72.76%—84.15%;其分子量分布较窄,为14.7—18.8 kDa,但不同坚果中oleosin亚型数量存在较大差异。钙调油体蛋白(caleosin)占膜蛋白总量的14.34%—24.96%,其在不同坚果中的分子量接近,为26.5—27.1kDa,且5种坚果中均只鉴定出一种caleosin构型。固醇油体蛋白(steroleosin)仅在核桃、薄壳山核桃和松子中被鉴定出,占膜蛋白总量的8.95%—12.89%。脂质组成方面,5种树坚果油体内部的甘油三酯组成差异较大,但膜磷脂组成近似。磷脂酰丝氨酸(PS)和磷脂酰胆碱(PC)是最主要的膜磷脂组分,两者合占膜磷脂总量的67.91%—75.06%。膜磷脂中不饱和脂肪酰基链比例高达69.64%—74.52%,且其中38.64%—45.15%的脂肪酰基均为油酸酰基。室温下榛子油体表现出最高的稳定性,储藏过程中,油体逐渐聚集并融合,同时伴随脂质氧化程度的升高,最终导致乳析现象的发生。【结论】5种树坚果以薄壳山核桃油体粒径最大,榛子油体稳定性最高。不同树坚果油体具有近似的膜蛋白和膜磷脂组成,但在oleosin异构体数量、油体内甘油三酯组成以及组分间比例上差异明显。其中,油体内脂质含量与oleosin的比例、油体膜磷脂与油体膜蛋白的比例可能对油体大小和稳定性具有重要影响。

药物小分子穿越磷脂双层膜输运过程中的时滞效应

本文基于扩散动力学,建立了一种新的药物小分子穿越磷脂双层膜输运的理论模型,研究药物小分子穿越磷脂双层膜输运的动态过程,考察药物小分子跨膜输运过程中的时间延迟(时滞)效应.研究发现,药物小分子在数分钟内穿越磷脂双层膜各区域进入细胞,由于时滞效应,穿膜过程呈现了周期性演化特性.当药物小分子数量增加到一定程度,磷脂分子层会出现微小孔,让积累的药物小分子快速通过.通过分析模型中各参数的敏感性,我们还发现,药物小分子在磷脂双层膜内不同区域的扩散特性,以及输运过程的时滞性,都会对药物小分子穿越磷脂双层膜的动力学有较大程度的影响.理论结果符合模拟、实验观测,进一步深刻揭示了药物小分子穿越磷脂双层膜的穿膜特性,可为设计确切的疗法药物提供必要的参考和新方案.

烟酸皮肤潮红反应用于抑郁症诊断的相关研究(综述)

抑郁症是一种以显著而持久的情绪低落、兴趣减退和快感缺失为主要症状的精神疾病;目前,由于抑郁症的高发病率、高自杀率、高复发率,如何准确有效的识别、干预抑郁症引起了重视。烟酸皮肤潮红测试是一种用于评估细胞膜中脂肪酸含量的简单方法;大量研究发现,抑郁症患者存在烟酸皮肤敏感度的显著降低,烟酸皮肤潮红反应钝化有望成为诊断抑郁症的辅助生物标志物。本文通过对国内外相关文献进行分析总结,重点对抑郁症中烟酸皮肤潮红反应的产生机制、检测方法以及研究进展3个方面展开论述,以挖掘该方法在辅助诊断抑郁中的价值,并期待能为今后更加深入的研究提供依据。

Significance of bilayer-forming phospholipids for skeletal muscle insulin sensitivity and mitochondrial function

Phosphatidylcholine(PC) and phosphatidylethanolamine(PE), which make up the bulk of mammalian cell membrane phospholipids, are recognized for their importance in metabolic health. Perturbations in the ratio of PC:PE can affect membrane integrity and function, which thus have serious health consequences. Imbalance in the hepatic PC and PE membrane content can be linked to metabolic disturbances such as ER stress, fatty liver and insulin resistance. Given that impaired insulin sensitivity underlies the pathology of many metabolic disorders and skeletal muscle is a significant regulator of energy metabolism, it is likely that aberrant phospholipid metabolism in skeletal muscle affects whole-body insulin sensitivity. Sarco/endoplasmic reticulum Ca^(2+) ATPase(SERCA) activity and mitochondrial function respond to alterations in PC:PE ratio and are associated with glucose homeostasis. Moreover, PC and PE content within the mitochondrial membrane influence mitochondrial respiration and biogenesis and thus, metabolic function. As skeletal muscle phospholipids respond to stimuli such as diet and exercise, understanding the implications of imbalances in PC:PE ratio is of great importance in the face of the rising epidemic of obesity related diseases. This review will summarize the current state of knowledge signifying the links between skeletal muscle PC:PE ratio and insulin sensitivity with respects to PC and PE metabolism, SERCA activity, mitochondrial function and exercise.

癌症中与脂质过氧化相关的铁死亡抑制机制

铁死亡(ferroptosis)是近年来发现的一种细胞死亡方式,以铁依赖和脂质过氧化(lipid peroxidation)为特点,有别于凋亡等其他细胞程序性死亡。诱导或促进细胞铁死亡也成为很有前景的肿瘤治疗方向。但在一些肿瘤中,癌细胞对铁死亡的敏感性下降,甚至顽固性抵抗死亡;除此之外,临床前实验中耐铁死亡诱导剂癌细胞的出现也引起隐忧。因此,明确肿瘤细胞抵抗铁死亡的机制,探索可能的靶向策略、削弱其对铁死亡的耐受程度,可以为肿瘤治疗提供帮助。铁死亡是在不同因素作用下,由活性氧产生、脂质过氧化、质膜受损和细胞死亡等系列事件组成的过程。其中,细胞质膜的脂质过氧化是铁死亡执行过程的核心阶段,对质膜的完整性、细胞存亡发挥决定性作用。本文将聚焦于这一关键事件,介绍其发生发展过程及其导致细胞死亡的可能机制,从膜磷脂组成、氧化级联反应、脂质过氧化物的清除和受损质膜的修复等方面,汇总近年来关于肿瘤细胞抑制脂质过氧化和抵抗铁死亡的研究进展,以及这些研究成果为提高肿瘤治疗效果提供的思路,为拓展铁死亡敏感性肿瘤的药物治疗、寻求铁死亡耐受肿瘤的药物治疗方案提供线索。

黄油乳清组分分析与乳化特性评价

黄油乳清(BS)是生产无水黄油时产生的副产物。由于富含乳脂肪球膜等组分,黄油乳清被认为是富集球膜组分的良好原料。然而,目前的研究集中于黄油乳清的基础组分构成,对脂肪球膜源组分的构成及应用特性的研究尚未明确,限制了黄油乳清的应用。通过离心搅打等方式从牛乳黄油中分离出黄油乳清,以原料乳和酪乳为对照,分析了黄油乳清的基本组分和脂肪球膜源组分构成。结果表明,与原料乳、酪乳相比,黄油乳清的蛋白质、脂肪质量分数显著增加,总钙含量显著降低,乳糖质量分数、含水率、pH值等无显著性差异(P>0.05);黄油乳清中含脂肪球膜磷脂56种,包括磷脂酰胆碱(Phosphatidylcholine, PC)20种、磷脂酰乙醇胺(Phosphatidylethanolamine, PE) 10种、磷脂酰丝氨酸(Phosphatidylserine, PS)7种、磷脂酰肌醇(Phosphatidylinositol, PI)6种、鞘磷脂(Sphingomyelin, SM)13种,其中鞘磷脂含量约为酪乳的3倍,质量浓度达到0.352 mg/mL;黄油乳清含脂肪球膜蛋白4种,其中丰度最大的为高碘酸希夫糖蛋白6/7,球膜蛋白占总蛋白的23.32%,是酪乳的1.1倍;对脱脂乳、酪乳和不同浓度黄油乳清乳化特性进行比较,研究结果显示,黄油乳清乳化性显著优于同浓度酪乳(P<0.05);在添加量3%时,黄油乳清乳化活性指数和乳化稳定性指数达到最大,分别为2.682 m2/g和91.1%。综上,黄油乳清中含丰富的脂肪球膜源组分,同浓度下,黄油乳清乳化特性优于酪乳,具有较高的应用潜力。

胆固醇与含PUFA磷脂作用的分子动力学影响研究

通过分子动力学研究了胆固醇对含有PUFA的SDPC磷脂双层膜的影响,引入了单不饱和的SOPC磷脂膜进行对比。模拟结果表明,加入胆固醇能够提高脂膜的有序度,增加脂膜的厚度。该效果在胆固醇的摩尔浓度为25%左右增大了两种磷脂的差异,在50%左右差异减小。通过对胆固醇周围最近邻磷脂链密度的分析发现,低饱和度的DHA链影响了SDPC中饱和链与胆固醇的相互作用,说明一定浓度下的胆固醇可能通过对PUFA微区性质的调节,促进细胞膜中不同饱和度磷脂的液相分离。

一种新的磷脂分子膜界面分子动力学模拟

翻转磷脂分子是把中性磷脂分子的磷酸基团和胆碱基团的位置互换后人工合成的新磷脂分子。本文运用分子动力学方法研究磷脂的亲水带电基团在膜内不同位置时对膜界面的水分子的分布和结构的影响。结果发现翻转磷脂双层膜的磷酸基团周围水分子数目增加,而其胆碱基团周围水分子数目却是减少了。翻转磷脂膜界面的水分子平均偶极取向与自然的磷脂膜界面的水分子平均偶极取向是相反的,而与胆碱基团相关的水分子平均偶极取向也发生了逆向。

Interaction of SynaptotagminⅠ with Phospholipid Membrane: A Monolayer Study

Synaptotagmin Ⅰ(sytⅠ) is an abundant integral membrane protein of the synaptic vesicle and the C2A domain is an important functional domain in the cytoplasmic part of sytⅠ. C2A prefers to interact with plasmic membranes of neuron cells in vivo and such interaction is closely related to the sytⅠ physiological function as a Ca 2+ sensor in the Ca 2+ regulated neurotransmitter release. However, the interaction nature between C2A and phospholipids is not well understood. Monolayers at an air/water interface were used to study the interaction between C2A and a phospholipid membrane. The results show that C2A preferentially inserts into the negatively charged phosphatidylserine monolayer and Ca 2+ ions are required for the interaction. Electrostatic force is mostly responsible for the insertion of C2A into dipalmitoyl phosphatidylserine monolayers.