Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sensitivity to lysis by complement of the erythrocytes of 56 patients with paroxysmal nocturnal haemoglobinuria (PNH) was compared to the membrane expression of decay accelerating factor (DAF, CD55), membrane inhibitor of reactive lysis (MIRL, CD59) and acetylcholinesterase (AChE). Most patients (36/50 72% in whom the analysis could be made) appeared to have erythrocytes of intermediate sensitivity to complement in the blood. These cells appeared as a discrete population of cells (PNH II cells), as a 'tail' of cells slightly less sensitive than the predominant PNH III cells (previously called PNH IIIb cells), or as a continuous spectrum of cells sensitive to complement. The PNH III cells totally lacked all three proteins (DAF, MIRL, AChE) by flow cytometric analysis whereas PNH I cells appeared to have normal or nearly normal amounts of each. The cells of intermediate sensitivity (PNH II) had coordinately decreased expression of all three proteins; the level of expression of DAF and MIRL paralleled the sensitivity of the cells to the haemolytic action of complement.
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PMID:The erythrocytes in paroxysmal nocturnal haemoglobinuria of intermediate sensitivity to complement lysis. 171 64

Membrane-associated decay accelerating factor (DAF) of human erythrocytes (Ehu) was analyzed for a C-terminal glycolipid anchoring structure. Automated amino acid analysis of DAF following reductive radiomethylation revealed ethanolamine and glucosamine residues in proportions identical with those present in the Ehu acetylcholinesterase (AChE) anchor. Cleavage of radiomethylated 70-kilodalton (kDa) DAF with papain released the labeled ethanolamine and glucosamine and generated 61- and 55-kDa DAF products that retained all labeled Lys and labeled N-terminal Asp. Incubation of intact Ehu with phosphatidylinositol-specific phospholipase C (PI-PLC), which cleaves the anchors in trypanosome membrane form variant surface glycoproteins (mfVSGs) and murine thymocyte Thy-1 antigen, released 15% of the cell-associated DAF antigen. The released 67-kDa PI-PLC DAF derivative retained its ability to decay the classical C3 convertase C4b2a but was unable to membrane-incorporate and displayed physicochemical properties similar to urine DAF, a hydrophilic DAF form that can be isolated from urine. Nitrous acid deamination cleavage of Ehu DAF at glucosamine following labeling with the lipophilic photoreagent 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine ([125I]TID) released the [125I]TID label in a parallel fashion as from [125I]TID-labeled AChE. Biosynthetic labeling of HeLa cells with [3H]ethanolamine resulted in rapid 3H incorporation into both 48-kDa pro-DAF and 72-kDa mature epithelial cell DAF. Our findings indicate that DAF and AChE are anchored in Ehu by the same or a similar glycolipid structure and that, like VSGs, this structure is incorporated into DAF early in DAF biosynthesis prior to processing of pro-DAF in the Golgi.
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PMID:Decay accelerating factor of complement is anchored to cells by a C-terminal glycolipid. 243 21

Paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes exhibit abnormalities in decay accelerating factor (DAF), acetylcholinesterase, and resistance to autologous C5b-9 attack. To investigate the nature of the lesion underlying PNH cells, we examined the relationship of these abnormalities to one another. Analyses of DAF in acetylcholinesterase-negative erythrocytes revealed that these two abnormalities involve functionally independent molecules, coincide precisely in the same cell populations, and are similarly expressed in PNH II and more complement-sensitive PNH III erythrocytes. The DAF and acetylcholinesterase deficiencies contrast with the C3b/C4b receptor (CR1) deficit, which is less profound and similarly distributed in complement-insensitive cell populations. Hemolytic studies showed that defective resistance to autologous C5b-9 attack is mediated by another mechanism. Whereas reconstitution of PNH II erythrocytes with DAF completely corrected their complement sensitivity, DAF reconstitution of PNH III erythrocytes restored their ability to circumvent C3b uptake but had no effect on their heightened susceptibility to reactive lysis. Assays of complement-insensitive (PNH I) erythrocytes surviving after reactive lysis disclosed partial DAF and acetylcholinesterase deficits. These findings indicate that the PNH lesion involves multiple membrane components and that PNH I erythrocytes are also abnormal.
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PMID:Relationship between decay accelerating factor deficiency, diminished acetylcholinesterase activity, and defective terminal complement pathway restriction in paroxysmal nocturnal hemoglobinuria erythrocytes. 243 44

1. We have studied the peripheral blood cells of an individual with the Inab phenotype who is deficient in decay accelerating factor (DAF). 2. In contrast with the situation in paroxysmal nocturnal haemoglobinuria, membranes from peripheral blood cells of the Inab phenotype individual lack DAF, but retain the other glycosylphosphatidylinositol-linked proteins acetylcholinesterase and LFA-3. 3. Unlike normal Epstein-Barr-virus-transformed lymphoblastoid cell lines (EBV-LCL), DAF was not expressed on EBV-LCL derived from peripheral blood lymphocytes of the Inab individual. 4. No differences in the DAF gene of normal and Inab phenotype individuals could be detected by Southern blotting studies. 5. EBV-LCL derived from the Inab individual had a gross reduction in the level of DAF mRNA compared with normal EBV-LCL. 6. Our results suggest that the DAF gene in the Inab phenotype contains a mutation which affects the transcription or processing of DAF mRNA.
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PMID:Studies on the defect which causes absence of decay accelerating factor (DAF) from the peripheral blood cells of an individual with the Inab phenotype. 247 16

Several proteins are attached to the cell membrane by a glycosyl-phosphatidylinositol (GPI) anchor. In this report, we show that during vesiculation of human RBCs in vitro, two of these proteins, acetylcholinesterase and decay accelerating factor, redistribute on the cell surface and become enriched in the released vesicles. As a result, the remnant cells are depleted of these proteins. We suggest that alterations in the architecture of the RBC membrane that precede vesiculation lead to selective polarization of GPI-anchored proteins within the domain of the membrane destined to become a vesicle. Since vesiculation occurs in many cell types, and if the loss of GPI-anchored proteins accompanies this process, it may have important biologic significance.
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PMID:Enrichment of two glycosyl-phosphatidylinositol-anchored proteins, acetylcholinesterase and decay accelerating factor, in vesicles released from human red blood cells. 247 79

Erythrocytes shed membrane vesicles in response to many stimuli. It has been previously demonstrated that glycan phosphatidylinositol-linked (GPI-linked) proteins such as decay accelerating factor and acetylcholinesterase are concentrated in these vesicles relative to the erythrocyte membrane. We have examined the requirement for GPI-linked proteins for the process of vesiculation. Erythrocytes that do not express GPI-linked proteins, obtained from patients with paroxysmal nocturnal hemoglobinuria (PNH), release between 10% and 50% of the quantity of vesicles as normal cells in response to the Ca2+ ionophore A23187. Platelets from the same patients produced 10% to 20% of the amount of vesicles as normal platelets. In addition, a mutant B-lymphoblastoid cell line that lacks GPI-linked molecules produces about half of the number of vesicles as compared with the wild-type cell line in response to the Ca2+ ionophore. Prior findings indicate that vesiculation is one of the mechanisms that the cell uses to remodel the plasma membrane, as well as protect itself from membrane-damaging agents such as the terminal complement components C5b-9. On the basis of the present results, we conclude that GPI-linked proteins play an important role in membrane vesiculation.
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PMID:Cells lacking glycan phosphatidylinositol-linked proteins have impaired ability to vesiculate. 767 19

The surface phosphatidylinositol (PI)-linked proteins on membrane of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes (PNHE) was analysed by a flowcytometer (FACS 420). It was found that the loss of acetylcholinesterase (AchE) and decay accelerating factor (DAF), two PI-linked proteins, from cell membrane of PNHE was not synchronous. The hemolysis rates of DAF (-) and AchE (-) PNHE were much higher than that of mixed population in cobra-venom factor (CoF) lysis test. Intact PNHE remaining after CoF lysis had relatively lower immunofluorescent labeling rate of AchE on membrane in comparison with normal erythrocytes. It implied that this subpopulation, in spite of being insensitive to complement lysis, was still abnormal in terms of the amount of PI-linked protein on cell membrane. When these intact PNHE remaining after CoF lysis were incubated with activated polymorphonuclear leukocytes (PMN) for three hours, immunofluorescent labeling of AchE on PNHE was prominently decreased. This indicated that reactive oxidants released from activated PMN might injure PI-linked proteins.
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PMID:Deficiency of phosphatidylinositol-linked membrane proteins on erythrocytes of different subpopulations in paroxysmal nocturnal hemoglobinuria. 769 84

Blood group antigens (BGAs) are chemical moieties on the red blood cell (RBC) membrane. Some BGAs (e.g., A, B, H, Lewis, P, I) are widely distributed throughout the body and may not be primarily erythroid antigens. Statistical correlations with ABO blood groups and disease have been made for years and have been highly controversial. It is not known if BGAs have a biological function. There are increasing reports of BGAs [e.g., Le(x) (an isomer of Le(a)), Le(y) (an isomer of Le(b)), T, Tn, "A-like"] appearing as "new" antigens on malignant tissue. Their presence and membrane density appears to correlate with the metastatic potential of the tumor. This often parallels loss of normal BGAs (e.g., ABH) from the tissue. Some of these antigens have been shown to influence the humoral and cellular response and have been used in assays to determine preclinical cancer, and in tumor immunotherapy. Interactions of some parasites and bacteria with human cells have been shown to depend on the presence of certain BGAs. P. vivax malarial parasites only enter human RBCs when the Fy6 Duffy blood group protein is present on the RBCs. Certain E. coli will only attach to the epithelial cells of the urinary tract if P or Dr BGAs are present in the epithelial cells. The P antigen is also the RBC receptor for Parvovirus B19. Leb has recently been found to be the receptor for H. pylori in the gastric tissue. The high frequency BGA, AnWj, is the RBC receptor for H. influenzae. BGAs have been shown to be associated closely with some important complement proteins. Ch/Rg BGAs have been found not to be true BGAs but are RBC-bound C4 (C4d). Knops/McCoy/York BGAs have been located on the C3b/C4b receptor (CR1). The high frequency BGAs of the Cromer (Cr) system are located on decay accelerating factor (DAF or CD55). Cartwright (Yt) BGAs are located on RBC acetylcholinesterase molecules. DAF and acetylcholinesterase are on phosphatidylinositol-glycan (PIG) linked proteins. When the PIG anchor is missing from RBCs, as in paroxysmal nocturnal hemoglobinuria, the affected RBCs lack all Cr, Yt, JMH, Hy/Gy, Do and Emm BGAs. The most important ligand for P, E and L selectins is sialyl-Le(x). This interaction is the tethering stage that start the leukocytes' journey from the circulation into the tissue. It appears that malignant cells may move through tissue in a similar way and may explain the close association of Le(x) with metastasis. Thus, there are increasing data suggesting a biological role for BGAs unrelated to the RBC.
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PMID:Blood group antigens as tumor markers, parasitic/bacterial/viral receptors, and their association with immunologically important proteins. 771 84

Human erythrocyte cell surface molecules that are attached to the cell membrane by glycosyl-phosphatidylinositol (GPI) anchors include the complement regulatory proteins decay accelerating factor (DAF, CD55) and membrane inhibitor of reactive lysis (MIRL, CD59), as well as the proteins that bear the Cartwright, Dombrock, and JMH blood group antigens. The acquired hematopoietic stem cell disorder paroxysmal nocturnal hemoglobinuria (PNH) results from the absence or marked deficiency in expression of GPI-anchored proteins in affected hematopoietic cells. PNH usually if not always results from a somatic mutation of an X-linked gene called PIG-A; the product of the PIG-A gene is a glycosyl transferase necessary for construction of the GPI anchor. DAF is a ubiquitously expressed protein present in many tissues, including gastrointestinal epithelia, corneal epithelia, and serosa of urinary and reproductive organs. DAF is a 70 kD glycoprotein containing complement regulatory short consensus repeats (SCRs); its gene is located in the regulation of complement activation (RCA) gene cluster on chromosome 1 and is about 40 kb in size. The Cromer blood group antigens, which reside on DAF, include 10 currently defined antigens, of which seven are of high incidence. The molecular basis of the Cr (a-) phenotype has been determined to be a single base pair substitution in DAF SCR4 (G-->C, leading to an ala193 to pro amino acid substitution). The Tc alpha antigen appears to be determined by the amino acid sequence of SCR1, with the Tc (a-b+) phenotype arising from a base pair substitution of G55-->T, leading to an arg18 to leu amino acid substitution. The null phenotype for Cromer antigens occurs when DAF is completely absent; only one example has been completely studied on the molecular level. That individual is homozygous for a point mutation in SCR1 (G314-->A) that creates a stop codon (TGA) in place of one normally encoding trp53 (TGG) and thus prevents further translation of the mRNA. The Dr(a-) phenotype expresses reduced quantities of DAF (approximately 40% of normal levels), as well as a polymorphism of DAF. Lack of the Dr alpha antigen has been proved to result from a single point mutation in SCR3 (C-->T in codon 165) that leads to a single amino acid substitution (ser-->leu). The Cartwright (Yt) antigens reside on acetylcholinesterase (AChE). In erythroid cells, a small exon that encodes the signal for attachment of the GPI anchor is retained in a tissue-specific process.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Glycosyl phosphatidylinositol-linked blood group antigens and paroxysmal nocturnal hemoglobinuria. 854 26

In the past few years, we have learned a great deal about the biologic function of structures bearing blood group antigens. Some blood group antigen-bearing proteins function as major transport channels within the erythrocyte membrane; these include the anion transporter (band 3: Diego and Wright antigens), the water channel (aquaporin: Colton antigens), and the urea transporter (Kidd antigens). At least two erythrocyte blood group antigen proteins have complement regulatory functions: the complement receptor type 1 (CR1, CD35: Knops antigens) and decay accelerating factor (DAF, CD55: Cromer antigens). Some blood group antigens reside on proteins with known receptor functions, such as the chemokine receptor (Duffy) and the hyaluronan receptor (Indian). The Cartwright antigens reside on an enzyme, acetylcholinesterase, and the Kell antigens reside on a protein that belongs to the CALLA-related family of neutral metalloproteinases. Finally, some blood group antigens reside on proteins that serve crucial structural functions necessary to normal erythrocyte lifespan and morphology. These proteins include band 3, glycophorins C/D (bearing the Gerbich antigens), and the Rh proteins. Both oligosaccharide and protein blood group antigens may act as receptors for bacterial, viral, and parasitic infectious agents.
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PMID:Biologic functions of blood group antigens. 937 20


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