The plasma membrane lipid composition affects fusion between cells and model membranes

Investigations were carried out on the effect of plasma membrane lipid modifications on the fusogenic capacity of control and ras-transformed fibroblasts. The plasma membrane lipid composition was modified by treatment of cells with exogenous phospholipases C and D, sphingomyelinase and cyclodextrin. The used enzymes hydrolyzed definite membrane lipids thus inducing specific modifications of the lipid composition while cyclodextrin treatment reduced significantly the level of cholesterol. The cells with modified membranes were used for assessment of their fusogenic capacity with model membranes with a constant lipid composition. Treatment with phospholipases C and D stimulated the fusogenic potential of both cell lines whereas the specific reduction of either sphingomyelin or cholesterol induced the opposite effect. The results showed that all modifications of the plasma membrane lipid composition affected the fusogenic capacity irrespective of the initial differences in the membrane lipid composition of the two cell lines. These results support the notion that the lipid composition plays a significant role in the processes of membrane-membrane fusion. This role could be either direct or through modulation of the activity of specific proteins which regulate membrane fusion.     

Evidence for the Presence of "Metabolic Sterols" in Pneumocystis: Identification and Initial Characterization of Pneumocystis carinii Sterols

Mixed life cycle stages of rat-derived Pneumocystis carinii were isolated from host lungs and their sterols were compared with those present in lungs from normal and immunosuppressed uninfected rats. Gas-liquid chromatography consistently detected, resolved, and quantified 9, 10, and 20 sterol components in the total nonsaponifiable neutral lipid fraction of lungs from normal rats, lungs from immunosuppressed uninfected rats, and P. carinii preparations, respectively. In all samples, cholesterol was the most abundant sterol present, comprising 97%, 93%, and 78% of total sterols in lungs from normal rats, lungs from immunosuppressed uninfected rats, and P. carinii , respectively. Tentative identifications of several rat lung and P. carinii minor sterols were made based on gas-liquid chromatogram retention times and fragmentation patterns from mass spectral analyses. Campesterol (ergost-5-en-3-ol), cholest-5-en-3-one, and β -sitosterol (stigmast-5-en-3-ol) were among the minor components present in both types of lung controls, and were also components of P. carinii sterols. In contrast to lung controls, the sterols of P. carinii were enriched in C₂₈ and C₂₉ sterols with one or two double bonds, and a hydroxyl group at C-3 (ergost-5-en-3-ol, ergost-7-en-3-ol, ergosta-dien-3-ol, stigmast-5-en-3-ol, stigmast-7-en-3-ol and stigmasta-dien-3-ol). Steryl esters of P. carinii , probably stored in cytoplasmic lipid droplets, were dominated by those present in the host lung. In separate studies. 3-hydroxy-3-methylglutaryl coenzyme A activity, a key enzyme in the regulation of sterol biosynthesis, was detected in purified P. carinii preparations and incorporation of radiolabeled squalene and mevalonate was observed. Together, these results suggest that the parasite readily takes up and incorporates host sterols, and that the organism synthesizes some of its own "metabolic sterols"     

Schistosoma mansoni: Phospholipid nature of the “agglutinin”

The haemagglutinating activity of the membrane-associated Schistosoma mansoni “agglutinin” is mainly due to acidic phospholipids, particularly phosphatidylinositol and phosphatidylserine. The role of these phospholipids in possible lipid-protein interactions in the host-parasite relationship is discussed.     

Scavenger receptors for oxidized and glycated proteins

Summary. Our present knowledge on chemically modified proteins and their receptor systems is originated from a proposal by Goldstein and Brown in 1979 for the receptor for acetylated LDL which is involved in foam cell formation, one of critical steps in atherogenesis. Subsequent extensive studies using oxidized LDL (OxLDL) as a representative ligand disclosed at least 11 different scavenger receptors which are collectively categorized as scavenger receptor family. Advanced glycation endproducts (AGE) and their receptor systems have been studied independently until recent findings that AGE-proteins are also recognized as active ligands by scavenger receptors including class A scavenger receptor (SR-A), class B scavenger receptors such as CD36 and SR-BI, type D scavenger receptor (LOX-1) and FEEL-1/FEEL-2. Three messages can be summarized from these experiments; (i) endocytic uptake of OxLDL and AGE-proteins by macrophages or macrophage-derived cells is mainly mediated by SR-A and CD36, which is an important step for foam cell formation in the early stage of atherosclerosis, (ii) selective uptake of cholesteryl esters of high density lipoprotein (HDL) mediated by SR-BI is inhibited by AGE-proteins, suggesting a potential pathological role of AGE in a HDL-mediated reverse cholesterol transport system, (iii) a novel scavenger receptor is involved in hepatic clearance of plasma OxLDL and AGE-proteins.     

Disruption of the murine protein kinase Cbeta gene promotes gallstone formation and alters biliary lipid and hepatic cholesterol metabolism

The protein kinase C (PKC) family of Ca(2+) and/or lipid-activated serine-threonine protein kinases is implicated in the pathogenesis of obesity and insulin resistance. We recently reported that protein kinase Cβ (PKCβ), a calcium-, diacylglycerol-, and phospholipid-dependent kinase, is critical for maintaining whole body triglyceride homeostasis. We now report that PKCβ deficiency has profound effects on murine hepatic cholesterol metabolism, including hypersensitivity to diet-induced gallstone formation. The incidence of gallstones increased from 9% in control mice to 95% in PKCβ(-/-) mice. Gallstone formation in the mutant mice was accompanied by hyposecretion of bile acids with no alteration in fecal bile acid excretion, increased biliary cholesterol saturation and hydrophobicity indices, as well as hepatic p42/44(MAPK) activation, all of which enhance susceptibility to gallstone formation. Lithogenic diet-fed PKCβ(-/-) mice also displayed decreased expression of hepatic cholesterol-7α-hydroxylase (CYP7A1) and sterol 12α-hydroxylase (CYP8b1). Finally, feeding a modified lithogenic diet supplemented with milk fat, instead of cocoa butter, both increased the severity of and shortened the interval for gallstone formation in PKCβ(-/-) mice and was associated with dramatic increases in cholesterol saturation and hydrophobicity indices. Taken together, the findings reveal a hitherto unrecognized role of PKCβ in fine tuning diet-induced cholesterol and bile acid homeostasis, thus identifying PKCβ as a major physiological regulator of both triglyceride and cholesterol homeostasis.     

Trypanosoma cruzi: Participation of cholesterol and placental alkaline phosphatase in the host cell invasion

One of the most important parasitic endemic diseases in Latin America is Chagas disease, with almost 20 million people being infected and 60 million others at risk of infection. In the cell infection by Trypanosoma cruzi, the first step is contact with the host cell by receptors and ligands on the membrane. It is known that lipids play an important role in the interaction process between pathogens and host cells with lipid rafts being highly specialized regions of the plasma membrane that are enriched in cholesterol and sphingolipids. We explored whether the treatment with methyl-beta-cyclodextrin alone or by adding Mevinolin, an inhibitor of cholesterol synthesis could deplete membrane cholesterol of the HEp2 cell and if this treatment could affect the trypomastigote infection into the host cell. These treatments led to a leakage of cholesterol, and concomitantly, PLAP enzyme and unidentified proteins resulting in a decrease of the invasion process. However, the GGTP enzyme was not liberated from the host cell membranes.     

A comparison of the behavior of cholesterol and selected derivatives in mixed sterol-phospholipid Langmuir monolayers: a fluorescence microscopy study

Eukaryotic cells require sterols to achieve normal structure and function of their plasma membranes, and deviations from normal sterol composition can perturb these features and compromise cellular and organism viability. The Smith-Lemli-Opitz syndrome (SLOS) is a hereditary metabolic disease involving cholesterol (CHOL) deficiency and abnormal accumulation of the CHOL precursor, 7-dehydrocholesterol (7DHC). In this study, the interactions of CHOL and the related sterols desmosterol (DES) and 7DHC with l-alpha-dipalmitoylphosphatidylcholine (DPPC) monolayers were compared. Pressure-area isotherms and fluorescence microscopy were used to study DPPC monolayers containing 0, 10, 20, or 30 mol% sterol. Similar behavior was noted for CHOL- and DES-containing DPPC monolayers with both techniques. However, while 7DHC gave isotherms similar to those obtained with the other sterols, microscopy indicated limited domain formation with DPPC, indicating that 7DHC packs somewhat differently in DPPC membranes compared to CHOL and DES. These results are discussed in relation to SLOS pathobiology.     

蓖麻“哲蓖三号”主要数量性状遗传参数研究

蓖麻“哲蓖三号”主要数量性状遗传参数研究张春华包红霞（内蒙古哲里木盟农业科学研究所,通辽０２８０１５）ＳｔｕｄｉｅｓｏｎｔｈｅＨｅｒｅｄｉｔａｒｙＰａｒａｍｅｔｅｒｓｏｆＭａｊｏｒＱｕａｎｔｉｔａｔｉｖｅＣｈａｒａｃｔｅｒｓｏｆＣａｓｔｏｒ“ＺＨＥＢ...     

The contribution of urbanization to non-communicable diseases: Evidence from 173 countries from 1980 to 2008

It is widely believed that the expanding burden of non-communicable diseases (NCDs) is in no small part the result of major macro-level determinants. We use a large amount of new data, to explore in particular the role played by urbanization – the process of the population shifting from rural to urban areas within countries – in affecting four important drivers of NCDs world-wide: diabetes prevalence, as well as average body mass index (BMI), total cholesterol level and systolic blood pressure. Urbanization is seen by many as a double-edged sword: while its beneficial economic effects are widely acknowledged, it is commonly alleged to produce adverse side effects for NCD-related health outcomes. In this paper we submit this hypothesis to extensive empirical scrutiny, covering a global set of countries from 1980–2008, and applying a range of estimation procedures. Our results indicate that urbanization appears to have contributed to an increase in average BMI and cholesterol levels: the implied difference in average total cholesterol between the most and the least urbanized countries is 0.40 mmol/L, while people living in the least urbanized countries are also expected to have an up to 2.3 kg/m² lower BMI than in the most urbanized ones. Moreover, the least urbanized countries are expected to have an up to 3.2 p.p. lower prevalence of diabetes among women. This association is also much stronger in the low and middle-income countries, and is likely to be mediated by energy intake-related variables, such as calorie and fat supply per capita.     

Oral administration of the biomimetic [Cr3O(O2CCH2CH3)6(H2O)3]+ increases insulin sensitivity and improves blood plasma variables in healthy and type 2 diabetic rats

The in vivo effects of gavage administration of the synthetic, functional biomimetic cation [Cr₃O(O₂CCH₂CH₃)₆(H₂O)₃]⁺ to healthy and type 2 diabetic model rats are described. After 24 weeks of treatment (0–1,000 g Cr/kg body mass) of healthy Sprague Dawley rats, the cation results in a lowering (P<0.05) of fasting blood plasma low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and insulin levels and of 2-h plasma insulin and glucose concentrations after a glucose challenge. Zucker obese rats (a model of the early stages of type 2 diabetes) and Zucker diabetic fatty rats (a model for type 2 diabetes) after supplementation (1,000 g Cr/kg) have lower fasting plasma total, high-density lipoprotein, and LDL cholesterol, triglycerides, glycated hemoglobin, and insulin levels and lower 2-h plasma insulin levels in glucose tolerance tests. The lowering of plasma insulin concentrations with little effect on glucose concentrations suggests that the supplement increases insulin sensitivity. The cation after 12 and 22 or 24 weeks of administration lowers (P<0.05) fasting plasma glycated hemoglobin levels in the Zucker diabetic and Zucker obese rats, respectively, and thus can improve the glucose status of the diabetic models. The effects cannot be attributed to the propionate ligand.Supplementary material is available for this article at .An erratum to this article can be found at