Saturday, 17 June 2017

Lysophosphatidylcholine kháng Raji

Hoạt tính độc tế bào của Lysophosphatidylcholine

https://www.karger.com/Article/PDF/216779

Lysophosphatidylcholine kháng Raji

From Wikipedia, the free encyclopedia
General chemical structure of lysophosphatidylcholines, where R is a variable fatty acid chain
Lysophosphatidylcholines (LPC, lysoPC), also called lysolecithins, are a class of chemical compounds which are derived from phosphatidylcholines.

Overview[edit]

They result from partial hydrolysis of phosphatidylcholines, which removes one of the fatty acid groups. The hydrolysis is generally the result of the enzymatic action of phospholipase A2.[1] Among other properties, they activate endothelial cells during early atherosclerosis[2] and stimulate phagocyte recruitment when released by apoptotic cells.[3] Moreover, LPCs can be used in the lab to cause demyelination of brain slices, to mimic the effects of demyelinating diseases such as multiple sclerosis. Further, they are known to stimulate phagocytosis of the myelin sheath and can change the surface properties of erythrocytes.[4] LPC-induced demyelination is thought to occur through the actions of recruited macrophages and microglia which phagocytose nearby myelin. Invading T cells are also thought to mediate this process. Bacteria such as Legionella pneumophila utilize phospholipase A2 end-products ( fatty acids and lysophospholipids) to cause host cell (macrophage) apoptosis through cytochrome C release.
LPCs are present as minor phospholipids in the cell membrane (≤ 3%) and in the blood plasma (8-12%).[4] Since LPCs are quickly metabolized by lysophospholipaseand LPC-acyltransferase, they last only shortly in vivo. By replacing the acyl-group within the LPC with an alkyl-group, alkyl-lysophospholipids (ALP) were synthesized. These LPC analogues are metabolically stable, and several such as edelfosine, miltefosine and perifosine are under research and development as drugs against cancer and other diseases.[4][5] Lysophosphatidylcholine processing has been discovered to be an essential component of normal human brain development: those born with genes that prevent adequate uptake suffer from lethal microcephaly.[6]
LPCs occur in many foods naturally. In Starch: Chemistry and Technology third edition on page 592, the authors state that “lysophosphatidylcholine makes up about 70% of the lipids in oat starch.” [7]
Their anti-cancer abilities are special since they do not target the cell DNA but insert into the plasma membrane and cause apoptosis through influencing several signal pathways. Therefore, their effects are independent of the proliferation state of the tumor cell.[8]

Other Names for Phosphatidylcholine in Food, Products, and Industry[edit]

Lysolecithin is a name used prior to the 1980s that was lost and now is found as lysophosphatidylcholine. In addition to several other names lysolecithin / lysophosphatidylcholine is also called hydrolyzed lecithin or hydrolysed lecithin or enzyme-modified lecithin. It is often shortened to LPC or lysoPC. The demyelinating effects of lysolecithin / lysophosphatidylcholine occur through topical application [9] and injection.[10]
Lysophosphatidylcholine could be the lost link in the Multiple Sclerosis controversy between the neurologists and the vascular surgeons since lysophosphatidylcholine has a twofold inflammation effect - lysophosphatidylcholine causes lesions on the central nervous system [11] and lysophosphatidylcholine causes vasoconstriction in the venous system.[12] More is discussed below concerning possible diseases related to excessive intake of lysophosphatidylcholine. If one has sclerosis or venous occlusion then one may want to try removing all sources of lysophosphatidylcholine as seen in these foods and products.
In the Biochemistry of Foods, Peter Eck explains recombinant DNA technologies in food. Pages 543-545 explain the use of glycerophospholipid cholesterol acyltransferase and the reaction products which are lysophospholipids. He states that “the enzyme preparation is used in egg yolk and whole eggs, in processed meats, in degumming of vegetable oils, in milk products such as cheese, and in bakery products containing eggs, such as cake products.” Then he lists each one and that in milk, the enzyme produces lysophospholipids from the phospholipids. He further explains that the enzyme preparation converts phospholipids to lysophospholipids in each of the above areas. Lysophosphatidylcholine is a lysophospholipid. This is significant and shows that there are unnaturally high amounts of lysophosphatidylcholine in enzyme-modified foods.[13]

Foods and Products with Unnaturally High Quantities of Lysophosphatidylcholine[edit]

Modified coconut oil has high levels of lysophosphatidylcholine; look at Mr. Rahman’s page 12 chart [14] to see that naturally phosphatidylcholine is 34 percent of lipids in coconut oil and lysophosphatidylcholine is only four percent. Once modified though, all that phosphatidylcholine could become hydrolyzed and be lysophosphatidylcholine – a demylenating toxin. In 2012, there was a lot said about modified coconut oil’s benefits for tooth brushing.
Here is another use for lysophosphatidylcholine – an immune activator. Vaccines.[15]

Diseases Related to Excessive Intake of Unnatural Quantities of Lysophosphatidylcholine[edit]

What effects would occur from lysophosphatidylcholine in or near the eye? Hypothetically, one suffering from macular degeneration may drop lysophosphatidylcholine, a demyelinating agent, in one's eyes. This would make the retinal vein occlude due to the vasoconstricting effects of lysophosphatidylcholine and could cause wet macular degeneration; conversely, if one is not taking a demyelinating agent into or around one's eye, then one would have dry macular degeneration and no retinal occlusion.
More research needs to be done to look into this hypothesis and as Ebrahimi and Handa said about lipid biology, “While lipoproteins in Bruch’s membrane both accumulate and can become oxidized, experimental proof of establishing how lipoprotein accumulation in Bruch’s membrane leads to RPE cell death or drusen formation is currently lacking and would establish a definitive role for lipids in AMD. In the future, it will be necessary for the epidemiologists, genetics, and molecular and cellular biologists to work together to definitively determine how lipid biology influences the development of AMD. It is hoped that greater understanding of the molecular biology of AMD lesions will provide a knowledge based on which to develop multiple treatment targets for the benefit of patients with AMD.” [16] Further study needs to be done to determine if the vasoconstriction could be reduced and the vein brought back to normal functioning by eliminating any demyelinating agents in foods, drops, or products.
In the Journal of Viral Hepatitis, Nie and Han et al. researched 99 metabolites in Acute-on-chronic liver failure and found, “Our study demonstrated the following 17 metabolites, including LysoPC(18:0), LysoPC(17:0), LysoPC(16:0), LysoPC(15:0), LysoPC(14:0), L-Threonine, Acetoacetic acid, DHAP(18:0), Phenylalanyl Phenylalanine, Bilirubin glucuronide, PA(20:4(5Z,8Z,11Z,14Z)e/2:0),m/z = 210.05, m/z = 475.172, m/z = 797.3, m/z = 599.29, m/z = 258.818 and m/z = 775.318. These 17 metabolites could be used as important potential markers for predicting the prognosis of patients with HBV-related ACLF. 11 metabolites, including LysoPC(14:0), Phenylalanyl Phenylalanine, Bilirubin glucuronide, LysoPC(22:5), m/z = 797.3, m/z = 759.286, m/z = 475.172, m/z = 599.29, m/z = 515.313, m/z = 775.318 and m/z = 809.287 showed disease-monitoring value.” This breakthrough research shows that in the acute-on-chronic liver failure the lysophosphatidylcholine and the mechanisms that directly surround it play a huge part in downfall. The other 82 metabolites studied in this paper do not have negative numbers. The LPCs are the ones implicated in liver cirrhosis and hepatitis.
Along the same lines, Neiderhiser and Maksem proved that ethanol (drinking alcohol) increases lysophosphatidylcholine absorption in the stomach.[17] Perhaps, ingesting unnaturally large amounts of lysoPC in addition to large amounts of alcohol is the cause of alcoholic liver disease.

Lysophosphatidylcholine - The Reason Why Smoking is Bad for those with Multiple Sclerosis[edit]

It is well known that smoking tobacco makes multiple sclerosis worse [18] although none can explain why, until now. Pasini and group at the University of Verona found that smoking induces phospholipase and increases lysoPC levels,[19] which makes lesions in high numbers. Pasini et al. said, “…smokers compared to non-smokers, had significantly higher levels of circulating oxLDL (44.7±9.1 versus 15.8±7.5 µg/ml respectively, P<0.001). Moreover our results showed higher plasma levels of Lp-PLA2 (256.7±63.1 versus 191.3±48.0 ng/ml respectively, P<0.001) and of lysoPC (133.8±39.4 µmol/l and 95.3±20.8 µmol/l respectively, P<0.001) in smokers compared to non-smokers. These data are presented in Table 1. We also found a significant positive correlation between plasma concentrations of ox-LDL and of LpPLA2 (r=0.654, P<0.001) and between plasma concentrations of Lp-PLA2 and of lysoPC in the whole population of subjects studied (r=0.639, P<0.001),” They went on to say, ”Moreover the correlation between lysoPC and CIMT together with the finding that lysoPC up-regulates proteoglycan synthesis suggests that lysoPC may be a link between smoking and intimal thickening.” Hypothetically, the reason not every smoker has MS may be due to a cumulative effect of lysoPC, which would depend on what foods and products everyone’s using.

See also[edit]

Posted by at No comments:

Raji cell

Raji cell

From Wikipedia, the free encyclopedia
Raji cell culture.
Raji cell line is the first continuous human cell line from hematopoietic origin.[1] The cell lines produce an unusual strain of Epstein-Barr virus which will both transform cord blood lymphocytes and induce early antigens in Raji cells. Translocations between chromosomes 8 and 22 have occurred in all three lines, but the cells synthesize immunoglobulin M with light chains of the kappa type, in contrast to the usual concordance between a translocation involving chromosome 22 and lambda chain synthesis. Both kappa genes and one lambda gene are rearranged. These findings indicate either that translocation may occur as a separate event from immunoglobulin gene rearrangement or that the proposed hierarchical sequence of immunoglobulin gene rearrangements is not always adhered to. The data also imply that in cells containing a translocation between the long arm of chromosome 8 and a chromosome bearing an immunoglobulin gene, alteration of cellular myc expression may occur regardless of the immunoglobulin gene that is expressed.[2] Raji cell is widely used as a transfection host and also to understand the hematopoietic and other cell malignancies. It also used for detection of immune complex because it possesses and expresses several receptors for certain complement components, as well as Fc receptors for immunoglobulin G.[3]

Background[edit]

Based on the morphological characteristic, this cell is categorized as lymphoblast-like.[4] This suspension cell is derived from B-lymphocyte of an 11-year-old Nigerian Burkitt's lymphoma male patient in 1963. R.J.V. Pulvertaft is the first person who established this cell line.[4] The culture medium used to grow this cell line is RPMIsupplemented with serum. Some characteristics of Raji cell is lack of differentiation thus shows the formation of large aggregations consist of hundreds individual cells. The cells are relatively large in diameter (5-8 μm), have irregular indented nuclei, and almost extensive cytoplasm with free ribosomes which tend to clump.[5] Raji cell grows as single, non-motile, free-floating (non-adhesion) individuals or doublets to glass. Some cells look elongated like pear-shaped with larger, multinucleate, round cells.[5]
Raji cell is widely used as a transfection host and also to understand the hematopoietic and other cell malignancies. It also use for detection of immune complexbecause it possesses and expresses and lots of receptors for certain complement components, as well as Fc receptors for immunoglobulin G.[3]

Description[edit]

A cell of a cultured line of lymphoblastoid cells derived from a Burkitt lymphoma; it possesses numerous receptors for a certain complement components and is thus suitable for use in detection of immune complexes. It expresses certain complement receptors as well as Fc receptors for immunoglobulin G.[6]

Raji Cell Line Human[edit]

-Biological source --> Lymph from human
-Description --> Human Black, Burkitt's lymphoma
-Growth Mode --> Suspension
-Karotype --> 2n=46, diploid
-Morphology --> Lymphoblastoid
-Research Areas --> Kits/ Lysates/ Other -> Lysates -> Whole Cell Lysates -> Human[7]
-Shipped In --> Dry ice
-Storage Temperature --> -196 degrees C.[8] Raji cell slide can be stored for up to 6 months at 4 °C under desiccate conditions.

Raji Cell Binding Test[edit]

A test for the detection of soluble immunoglobulin (Ig)G-antigen complexes. Raji cells are a line EBV-transformed lymphocytes with surface Fc receptors. Complexes are detected by their ability to compete with a radiolabelled aggregated IgG for binding to cells.[citation needed]

Raji Cell Assay for Immune Complexes[edit]

Using a standard Raji assay employing 125I-IgG goat anti-human Fc gamma, the digestion of Raji cells with pronase reduced by 95% their ability to bind complement-fixed aggregated human gamma globulin and complement-fixed tetanus toxoid-antitetanus toxin complexes. However, binding at 37 degrees C of IgG from the sera of 16 patients with systemic lupus erythematosus (SLE) to pronase-digested Raji cells was reduced much less consistently and extensively (9-100% reduction; mean reduction of 51%). In more detailed studies of two SLE sera, sucrose density gradient centrifugation showed that greater than 50% of the IgG binding to undigested Raji cells sedimented in the 7S region. Pepsin digestion of immunoglobulin fractions from four SLE sera caused a reduction in SLE IgG binding to undigested Raji cells when detected with 125I anti-Fc gamma, but an increase when binding was detected with 125I-anti-Fab, suggesting that substantial SLE IgG can bind through F(ab')2 regions. Binding of IgG from SLE sera was not directed at neoantigenic sites induced by pronase digestion because binding activity was adsorbed with undigested cells as readily as with digested cells. Moreover, sera from 10 SLE patients that had negative Raji assays contained no IgG that bound to pronase-digested Raji cells. Meaning that, much of the IgG bound at 37 degrees C to Raji cells from the sera of many patients with SLE does not represent immune complexes but is probably antibody directed toward sites on the Raji cell.[9]

Raji cell Radio-immune Assay for Detecting Immune Complexes in Human Sera[edit]

A sensitivie and simple procedure for the detection and quantitation of soluble complement (C)- fixing immune complexes in sera of patients with various disease states has been developed by utilizing C receptors on Raji cells. These cells lack membrane-bound immunoglobulin but have receptors for IgG Fc, C3b, C3d, and possibly with other C proteins. Uptake experiments showed that both aggregated human gamma globulin (AHG) and 7S IgG bound to receptors for IgG Fc; however, AHG reacted with C bound to cells only via receptors for C and this binding was much more efficient than via IgG Fc receptors. AHG was used as an in vitro model of human immune complexes and its uptake by Raji cells was quantitated by 125I-radiolabeled antihuman IgG. The limit of sensitivity of this test was 6 mug AHG/ml serum. The ability of Raji cells to detect AHG in serum depended on the amount of radioactive antibody used and the size of aggregates. The presence of an excess of C somewhat inhibited binding of AHG containing C to Raji cells. The efficient binding of AHG by receptors for C on Raji cells was used for the detection and quantitation of immune complexes in human sera. Raji cells were incubated with sera to be tested and then reacted with excess radiolabeled antihuman IgG; the amount of radioactivity bound to the washed cells was determined and referred to a standard curve of radioactive antibody uptake by cells previously incubated with increasing amounts of AHG in serum. Thereby immune complexes were detected and quantitated in serum hepatitis, systemic lupus erythematosus, vasculitis, subacute sclerosing panencephalitis, dengue hemorrhagic fever, and malignancies.[10]
Posted by at No comments:
Subscribe to: Comments (Atom)