Lysophospholipid receptors in cell signaling.

There is increasing evidence that different phospholipids are involved in regulation of various cell processes and cell-cell interactions. Lysophospholipids (lysophosphatidic acid, lysophosphatidylcholine) and a number of lysosphingolipids play particular roles in these regulations. Their effects are mediated by specific G-protein-coupled receptors. G-Protein coupled signal transduction to the cell nucleus involving a chain of intracellular protein kinases induces the main effects in cells--growth, proliferation, survival, or apoptosis. This review summarizes recent data on various groups of lysophospholipid receptors and their cell signal transduction pathways.

Lipidomics: new approaches to the studies of cell signaling and prospects of use in medicine.

A new modern stage in the development of lipid biochemistry is presented: lipidomics, which emerged on the basic of new highly sensitive fractionation methods, primarily, mass spectroscopy. Lipidomics is defined mainly as systemic evaluation of all molecular types of lipids in an object, their cell functions, and molecules with which they react. Lipidomic approaches identifying picomole levels of individual lipids in combination with modern genome technology provide detailed information about the involvement of minor phospholipids in the cell signaling processes. Brief data on the functions of lysophospholipids as second messengers of signal transfer, their effects on cell processes, and possible involvement in the pathogenesis of some diseases are presented. It is expected that introduction of lipidomics in biomedical studies will promote the detection of targets for new drugs and development of new diagnostic tests.

Sphingolipids and cell signaling: involvement in apoptosis and atherogenesis.

This review considers various functional aspects of cell sphingolipids (sphingomyelin, ceramides) and lysosphingolipids (sphingosine-1-phosphate (S1P) and sphingosine phosphorylcholine). Good evidence now exists that they are actively involved in numerous cell-signaling processes. The enzymes responsible for formation and interconversion of cell sphingolipids (sphingomyelinases, ceramidase, sphingosine kinase, S1P-lyase) exhibit high sensitivity to various stimulating factors. This determines the content of individual cell sphingolipids and therefore the mode of cell response. Special attention is paid to preferential localization of sphingolipids in the rigid plasma membrane domains (rafts) coupled to many signal proteins. The suggestion is discussed that ceramide signaling may be based on the modification of fine molecular interactions in lipid rafts, resulting in its clusterization inducing the signal transduction. The review also highlights involvement of sphingolipids in cell proliferation, apoptosis, and in processes implicated to atherosclerosis.

[Membrane proteins and phospholipids as effectors of reverse cholesterol transport].

The review highlights the membrane aspect of cholesterol efflux from cell membranes to high density lipoproteins (HDL), an initial stage of reverse cholesterol transport to liver. Special attention is paid to ABC-A1 transporter and membrane SR-B1 receptor, their properties, putative mechanisms of action and their role in reverse cholesterol transport. Interaction of ABC-AI with plasma free apoA1 is suggested to facilitate the efflux of membrane phospholipids and formation of their complex with apoAI. Then this complex accepts the membrane cholesterol, with lipidation till the full HDL particle is formed. For a number of cells the correlation of cholesterol efflux into HDL with SR-BI expression was shown. The reversible binding of receptor SR-BI with HDL is supposed to influence molecular organization of membrane lipids, that promotes the efflux of cholesterol molecules out of the membrane.

Antiatherogenic effect of grape flavonoids in an ex vivo model.

The effects of grape phytoestrogens on cholesterol accumulation were studied in primary culture of human blood monocytes incubated with blood serum from postmenopausal women obtained before and 2, 4, and 6 h after single intake of plant components of grapes. Phytoestrogens from grape seeds, pressed out grapes, and fermented grape ridges prevent cholesterol accumulation in cells and can be regarded as prospective components for the development of natural preparations for the prevention of atherosclerosis in postmenopausal women.

[Hypolipoproteinemia and secondary role of atherosclerosis in the development of ischemic heart disease in patients with polycythemia vera].

Relationship between presence of coronary heart disease (CHD), coronary risk factors (parameters of lipid transport system and hypertension) and disturbances of microcirculation was studied in patients with myeloproliferative blood disease Polycythemia Vera (PV). Probability of tissue (including blood vessel wall) cholesterol accumulation was estimated by measurement of its content in skin surface layers. PV patients (n=55, including 27 patients with CHD) had predominant hypolipoproteinemia with normal proportion of various lipoprotein classes. Absence of substantial increase of skin surface cholesterol content both in patients with and without CHD was considered to be a sign of low probability of the presence of severe atherosclerotic processes. However patients with CHD had substantially more pronounced disturbances of microcirculation. Basing on these data the authors suggest that CHD in PV patients had non-lipoprotein genesis and present discussion of alternative mechanisms of vascular changes.

[Phosphatidylcholine as the basis for artificial pulmonary surfactants: comparison of surface active properties]. / Fosfatidilkholiny kak osnova iskusstvennogo legochnogo surfaktanta: sravnenie poverkhnostno-aktivnykh svoistv.

The Wilhelmy balance was used for in vitro testing of surface active properties of natural phosphatidylcholines (PCs) as possible basis for surfactant replacement therapy. Saturated PC, dipalmitoylphosphatidylcholine (DPPC) and phospholipon (PL) had similar parameters of surface activity: minimal values of equilibrium surface tension (EST) and the longest surface spreading time (SST). Unsaturated egg and soybean PCs also shared similar values of surface activity parameters (EST and SST). Correlation between fatty acid saturation of PCs and EST or SST allows to consider both these parameters as informative ones for surface tension evaluation in the search of components for artificial surfactant. Since parameters of DPPC and PL surface activity are equivalent in their performance, they may be potentially employed for testing instead of DPPC as a possible base for artificial surfactant.

[Relation between resistance to oxidation and cholesterol acceptance of high density lipoproteins in patients with ischemic heart disease]. / Vzaimosviaz' mezhdu okislitel'noi ustoichivost'iu i kholesterin-aktseptornoi sposobnost'iu lipoproteinov vysokoi plotnosti u bol'nykh ishemicheskoi bolezn'iu serdtsa.

Cholesterol (CH) acceptance ability of high density lipoproteins (HDL) was assessed in 43 ischemic heart disease (IHD) patients, including patients with post-infarction cardiosclerosis and class II-III effort angina. CH acceptance ability of HDL was measured as increment of HDL CH after incubation with artificial CH-containing system. Oxidabilities of HDL and total plasma were estimated by quantitation of lipid peroxidation products (hydroperoxides and thiobarbituric acid-reactive substances - TBARS) after incubation with Cu(2+) ions. HDL fraction (after apo B lipoproteins removal) of IHD patients appeared to include 2 times less additive CH compared with donor's HDL despite lower (-12%) HDL CH level. Negative correlation (r =-0.38, p<0.05) existed between formed TBARS in HDL and HDL CH acceptance. In total plasma of IHD patients elevation of both formed TBARS and particularly hydroperoxides was observed. Parallelism between decrease of CH acceptance by HDL, oxidability of HDL and of total plasma testifies on weakness not only of CH-accepting, but also of antioxidant HDL functions in IHD patients.

[The way of evaluation of cholesterol accepting capacity of plasma high density lipoproteins]. / Sposob otsenki kholestrin-aktseptornoi emkosti lipoproteinov vysokoi plotnosti plazmy krovi.

The simple way of quantitative evaluation of high density lipoproteins (HDL) capacity to absorb additive cholesterol quantity is proposed. It allows to evaluate indirectly intensity of the first, rate limiting stage of reverse cholesterol transport its accepting from the cells by means of HDL. The way includes the usage of stable artificial cholesterol donor--cholesterol covered inert polymer particles, which are than more convenient, than cell culture use. The total HDL rough fraction (i.e. serum after apoB lipoproteins removal) was shown to include more than 50% cholesterol in addition to yet presenting amount. But this ability is sharply reduced, or sometimes even is completely absent, in HDL of 63 coronary heart disease (CHD) patients (as compared with 41 healthy donors). This difference of potential cholesterol accepting capacity is revealed even at the same initial HDL concentrations. The negative correlation (r = - 0.32, p < 0.05) between this HDL property (delta HDL cholesterol) and their oxidability in the ions Cu2+ presence was observed. This underlines atherogenic role of HDL oxidability. The treatment of patients by phospholipids (as Lipostabyl) resulted to recovery of HDL cholesterol accepting capacity. The possible mechanisms of junction of this HDL activity with their oxidability are discussed, as well as necessity of evaluation of HDL properties and reverse cholesterol transport for the choice of care strategy of CHD patients.

[Erythrocyte cholesterol content in polycythemia vera: relation to ischemic heart disease]. / Soderzhanie kholesterina v éritrotsitakh pri istinnoi politsitemii: sviaz' s ishemicheskoi bolezn'iu serdtsa.

Relative cholesterol content and its distribution between erythrocytes and plasma were studied in 34 patients with polycythemia vera (PV) both with and without concomitant coronary heart disease (CHD). Deformability of erythrocytes, disturbances of microcirculation (blood flow fragmentation, decrease of capillary density) were also assessed. Erythrocytes cholesterol/phospholipids molar ratios (0.68+/-0.03) in patients was lower than normal value (0.8) in spite of decreased cell deformability. This was associated with some increase of peroxidation products. Blood cholesterol distribution between cell and plasma species had some peculiarities caused by high hematocrit: compared with normal value erythrocytes of patients carried relatively larger portion of total blood cholesterol (23.7+/-0.8% and 27-31%, respectively). However in CHD patients these values were significantly lower with correspondent increase of plasma cholesterol quota. This allowed to suggest possible protective role of blood cholesterol redistribution in polycythemia patients, through erythrocytes trafficking of some part of plasma cholesterol.

[Characteristics of the lipid transport system in psoriasis]. / Osobennosti lipid-transportnoi sistemy pri psoriaze.

Cholesterol of high density lipoprotein (HDL) subfractions (HDL2 and HDL3), activity of cholesterol ester transport protein (CETP), and standard lipoprotein parameters (cholesterol, triglycerides, HDL cholesterol) were measured in plasma of 192 patients with various psoriasis forms, which included simple "distributed psoriasis", erythrodermic and arthropathic psoriasis. Among psoriatic patients unusually high percent of persons with both hypo- and hyper-cholesterolemia was observed. The same situation was observed with frequency of cases with both low and high plasma HDL cholesterol levels, the distribution being depending from disease severity. In contrast to norm, psoriasis patients had big range not only in HDL2 cholesterol level, but also in HDL3 cholesterol. They also had decreased CETP activity. Data obtained suggest the existence of changes in reverse cholesterol transport system in psoriasis, which may influence skin cell proliferation (via control of cell supply with cholesterol).

Comparison of distribution characteristics of phosphatidylcholines and surfactant preparation.

Using the methods of surface balance we compared surface activity of different natural phosphatidylcholines. Dipalmitoylphosphatidylcholine, the principal component of natural surfactant, is characterized by less rapid spreading on the air-water interface compared to unsaturated yolk and soybean phosphatidylcholines, while the absolute rate of surface tension reduction was the same for all test lecithines. The surface activity of modified saturated soybean phosphadtidylcholine (Phospholipon) was similar to that of dipalmitoylphosphatidylcholine. The relationship between saturation of fatty acids in the molecule of phosphatidylcholine and the time of spreading on the air-water interface revealed in this study allows to use this parameter together with equilibrium surface tension for evaluation of surface activity when testing synthetic surfactant constituents.

[Effect of Fe2+ ions on the hemolysis induced by products of psoralen photo-oxidation]. / Vliianie ionov Fe2+ na gemoliz, indutsirovannyi produktami fotookisleniia psoralena.

The effects of Fe2+ ions on haemolysis induced by previously photooxidized psoralen (POP-haemolysis) were investigated. It was shown that POP-haemolysis was strongly activated by Fe2+ ions when ferrous ions were added to erythrocytes just after addition of POP. If POP was preincubated with Fe2+ before mixing with erythrocytes, then POP completely lost its ability to induce haemolysis. These data indicate the peroxidic nature of POP products responsible for haemolysis.

[Features of distribution of free and esterified cholesterol in the epidermis, biological membranes and plasma lipoproteins in psoriasis]. / Osobennosti raspredeleniia svobodnogo i éterifitsirovannogo kholesterina v épidermise, biomembranakh i lipoproteidakh plazmy pri psoriaze.

The parameters of cholesterol (CS) metabolism in the epidermis, blood plasma lipoproteins, and red cell membranes were assessed in patients with psoriasis. The levels of free and total CS in extracts from the surface of epidermis, in plasma lipoproteins, and in plasma triglycerides were measured, and the molar ratio CS/ phospholipids (CS/PL index) in red cell membranes assessed in 194 patients with psoriasis of different severity. The levels of free and total CS in the epidermis were found to increase as the psoriatic process grew in severity. These shifts manifested even in apparently intact skin sites, which indicated the primary nature of total-system disorders. As for the plasma lipids, statistically reliable changes were observed only for the relative level of free cholesterol of the plasma and, most of all, high-density lipoproteins. These values for the mean parameters in the five groups of examinees correlated (r from 0.71 to 0.92) with the levels of total and free CS in the epidermis. Contrary to it, the levels of total CS and triglycerides in the plasma had a tendency to decrease as the severity of the psoriatic process augmented. Such a trend was statistically reliable for the CS/PL index, which increased in all the patients except the most grave, this increase being the more, the less grave the disease was; this was manifested in an inverse correlation (r = 0.9, on average) with the epidermal CS. The detected uncommon relationship between CS values in the epidermis, plasma lipoproteins, and biological membranes indicates heretofore unknown features of metabolic disorders in psoriasis.