Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic lupus erythematosus (SLE) can produce profound disturbances in the central nervous system, characterized by encephalopathy, focal neurologic deficits, cerebral infarction, psychosis, and seizures. We used 31P nuclear magnetic resonance (NMR) spectroscopy to determine the in vivo levels of high-energy phosphates in the central nervous system of 10 patients with SLE and 10 age-matched normal controls. 31P NMR spectroscopy was performed on a 1.5-Tesla unit equipped with a dual-tuned 1H-31P surface coil and a software-directed DRESS (depth resolved surface coil spectroscopy) pulse sequence. This procedure detected ADP, ATP, sugar phosphates, phosphocreatine (PCr), inorganic phosphate, phosphomonoesters, and phosphodiesters in the brain tissue of all study subjects. Levels of ATP in the deep white matter of 10 SLE patients were significantly decreased compared with the levels in 10 normal controls, as quantitated by the ratio of ATP:ATP + ADP (mean +/- SD 0.81 +/- 0.11 versus 0.91 +/- 0.05; P less than 0.02). In a subgroup of 4 patients, PCr levels were decreased to a greater extent than the ATP levels. NMR spectroscopic alterations were not related to obvious anatomic lesions, as determined by standard cranial proton magnetic resonance imaging. In 4 SLE patients with markedly abnormal 31P NMR spectra, treatment with prednisone (80 mg/day) normalized the levels of ATP and PCr. Restoration of a normal 31P profile was accompanied by an obvious improvement in the patients' mental status and clinical symptoms. 31P NMR spectroscopy is a powerful new technique for monitoring high-energy phosphate metabolism, and may be particularly useful for characterizing central nervous system disease in patients with neuropsychiatric SLE.
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PMID:Depletion of high-energy phosphates in the central nervous system of patients with systemic lupus erythematosus, as determined by phosphorus-31 nuclear magnetic resonance spectroscopy. 236 38

Lipomodulin, purified to near homogeneity from rabbit peritoneal neutrophils, was phosphorylated by cyclic AMP-dependent protein kinase from bovine heart with concomitant loss of its ability to inhibit phospholipase A2 from porcine pancreas. Phosphorylation of lipomodulin was confirmed by the incorporation of 32P from [gamma-32P]ATP. To demonstrate that lipomodulin undergoes phosphorylation in vivo, rabbit peritoneal neutrophils were incubated with 32P and lipomoculin was isolated by immunoprecipitation with serum from a patient with systemic lupus erythematosus which has anti-lipomodulin antibody. Analysis of 32P-labeled immunoprecipitates by sodium dodecyl sulfate electrophoresis revealed a single peak of radioactivity that comigrated with [35S]methionine-labeled lipomodulin. The administration of a chemoattractant, N-formyl-methionyl-leucyl-phenylalanine to intact rabbit neutrophils, resulted in a marked increase in arachidonate release from the cells and an increase in 32P incorporation into lipomodulin. A close correlation was found between the extent of phosphorylation of lipomodulin and the rate of arachidonate release. Phosphorylation of lipomodulin in neutrophils gradually returned to the control level with corresponding cessation of arachidonate release. In contrast to the in vitro system, phosphorylation of lipomodulin and release of arachidonic acid from peptide-stimulated neutrophils required Ca2+ entry into the cells. These results suggest that the phosphorylation-dephosphorylation of lipomodulin, phospholipase inhibitory protein, is an important mechanism for chemotactic receptor-mediated regulation of arachidonic acid release in rabbit neutrophils.
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PMID:The regulation of lipomodulin, a phospholipase inhibitory protein, in rabbit neutrophils by phosphorylation. 626 23

Acquired abnormalities of platelet aggregation have been reported with increasing frequency. We studied five patients (including two with systemic lupus erythematosus and one with compensated chronic idiopathic thrombocytopenic purpura) in whom platelet aggregation responses to collagen, epinephrine and ADP are impaired; in all cases, we found that levels of platelet-associated immunoglobulin G (IgG) were increased. In all five patients substances stored in platelet-dense granules (ATP, ADP, serotonin and calcium) were diminished. The content of the alpha-granule substance, beta-thromboglobulin, was also decreased in most cases, whereas the levels of two secretable acid hydrolase enzymes (beta-glucuronidase and beta-N-acetyl glucosaminidase) were within normal limits. These findings are similar to those observed in subtypes of congenital storage pool deficiency. However, in contrast to the congenital disorder, a membrane-bound (nonsecretable) acid phosphatase was also decreased in the patients with acquired storage pool deficiency. These findings suggest that impaired platelet aggregation on an acquired basis may, in some patients, be due to immune platelet damage resulting in a distinctive type of platelet storage pool deficiency.
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PMID:Acquired storage pool deficiency with increased platelet-associated IgG. Report of five cases. 644 50

Purified RNA polymerase I was phosphorylated by the endogenous protein kinase or dephosphorylated by alkaline phosphatase and used as antigen in a radioimmunoassay with sera from systemic lupus erythematosus patients or serum from an immunized rabbit. Enzyme incubated in the absence of ATP or phosphatase served as control. Three to seven times more of the autoantibodies in the patients' sera reacted with phosphorylated RNA polymerase I than with control enzyme. The reactivity of the dephosphorylated enzyme with lupus autoantibodies was only 50-60% of that observed with control enzyme. Neither phosphorylation nor dephosphorylation of the enzyme had an effect on its reaction with the rabbit antibodies. The effect of phosphorylation on the reaction of each RNA polymerase I subunit (S1-S8; Mr = 190,000-17,000) with the patients' antibodies was determined by an immunoblot procedure following resolution of the subunits on polyacrylamide gels. Prior phosphorylation of the enzyme resulted in a dramatic increase in binding of each patient's antibodies to all polymerase subunits with the exception of S4. Anti-S4 antibody was not detected with either phosphorylated or control enzyme. Strikingly, antibodies in each patients' sera reacted with S6 only after its phosphorylation. Similarly, anti-S5 antibodies in the serum of one patient were only detected with phosphorylated RNA polymerase I. The present data suggest that at least a significant fraction of the anti-RNA polymerase I autoantibodies in the sera of systemic lupus erythematosus patients might be directed against phosphorylated sites on the enzyme and that phosphorylation may have a role in the production of this and other autoimmunogenic nuclear components which are hallmarks of this disease.
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PMID:Phosphorylation of RNA polymerase I augments its interaction with autoantibodies of systemic lupus erythematosus patients. 650 Dec 73

Vesicles released from human E by Ca(2+)-loading, ATP-depletion, or storage are enriched in several glycosylphosphatidylinositol-anchored proteins such as acetylcholinesterase (AchE) and decay-accelerating factor (DAF). As a result of this, the remaining E are depleted of these proteins. We analyzed whether vesiculation induced by ATP-depletion in vitro was also responsible for a loss of C receptor 1 (CR1), which is a transmembrane protein arranged predominantly in small clusters. ATP-depleted E had lost 15.4% to 33.9% of their CR1. This loss was similar to that of AchE and DAF. The released vesicles contained CR1. The number of CR1 per band 3 protein was 1.7 to 2.7 that in the original E, indicating an enrichment of CR1 in vesicles. This enrichment was similar to that observed for AchE and DAF (1.83- and 2.6-fold, respectively). The capacity of the vesicles and the ATP-depleted E to bind C3b-coated immune complexes correlated with the CR1 number, suggesting that there was no preferential loss of CR1 clusters. Vesicles released from human E during C attack also contained CR1. In conclusion, in vitro aging induced by ATP-depletion is responsible not only for a loss of glycosylphosphatidylinositol-anchored proteins, but also of CR1. Whether vesiculation explains the loss of CR1 from aging E in vivo and from E of patients with SLE or AIDS remains to be studied.
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PMID:Release of vesicles enriched in complement receptor 1 from human erythrocytes. 832 33

Stress or heat-shock proteins may be involved in the initiation and perpetuation of autoimmune diseases. In order to investigate a possible role of autoantibodies against the 70-kD family of heat-shock proteins in systemic lupus erythematosus (SLE), sera of SLE patients and healthy subjects were tested for the presence of IgG and IgM antibodies to 70-kD class proteins. These proteins were purified by affinity chromatography on ATP-agarose and used in Western blotting studies. The data obtained revealed that antibodies to the 72-kD and the 73-kD heat-shock proteins occurred with similar frequencies both in healthy subjects and SLE patients. Thus, approximately 20% of the sera in each group contained IgG antibodies, and IgM antibodies were detected in about 30% of the sera tested. Moreover, in SLE patients no association between the occurrence and titre of these antibodies and disease activity was found. These data suggest that antibodies to the 70-kD class heat-shock proteins are naturally occurring and argue therefore against an involvement of these antibodies in the pathogenesis of SLE.
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PMID:Similar frequency of autoantibodies against 70-kD class heat-shock proteins in healthy subjects and systemic lupus erythematosus patients. 846 63

The two leaflets of the plasma membrane of eukaryotic cells differ in lipid composition: the outer leaflet comprises mainly neutral choline containing phospholipids, whereas the aminophospholipids reside almost exclusively in the cytoplasmic leaflet. The importance of transmembrane lipid asymmetry may be judged from the fact that the cell invests energy to maintain this situation for which at least two regulatory mechanisms are held responsible. A translocase, selective for aminophospholipids, acts as an ATP-dependent pump for rapid inward movement of phosphatidylserine (PS) and phosphatidylethanolamine; in addition, a non-selective, but also ATP-dependent pump causes outward movement of phospholipids, be it at a much lower rate compared to the inward transport by the aminophospholipid translocase. These two systems, acting in concert, are thought to be the main players in the maintenance of a dynamic equilibrium of the phospholipids over both membrane leaflets. Dissipation of membrane lipid asymmetry can be elicited in different cell types under a variety of conditions; in particular, platelets upon activation rapidly lose their normal plasma membrane lipid distribution, but also in other blood cells, lipid asymmetry can be lost, be it at a much lower rate and extent than in platelets. A putative protein, referred to as "scramblase' has been described, which requires the continuous presence of elevated intracellular Ca(2+)-levels, to allow a rapid, non-selective and bidirectional transbilayer movement of phospholipids. Although scrambling of lipids does not require ATP as such, preliminary studies suggest the possible involvement of one or more phosphorylated proteins. The most prominent consequence of the loss of phospholipid asymmetry is exposure of PS in the outer leaflet of the plasma membrane. Surface-exposed PS serves several important physiological functions: it promotes assembly of enzyme complexes of the coagulation cascade, it forms a signal for cell-cell recognition, which is important for cell scavenging processes. Surface-exposure of PS is an early phenomenon of apoptosis and appears to be involved in efficient removal of these cells. In addition, PS in the outer leaflet of cells is thought to play a role in cell fusion processes. It may be clear from the foregoing, that the amount of PS present at the cell surface needs to be tightly controlled, and that an impairment of this process leads to either excessive- or diminished exposition of PS which may have several pathophysiological consequences.
Lupus 1996 Oct
PMID:Regulatory mechanisms in maintenance and modulation of transmembrane lipid asymmetry: pathophysiological implications. 890 87

A new radial enzyme diffusion (RED) method for the measurement of DNase activity in serum and urine is described. The sensitivity of the assay is in the range of 15.6-500 ng/ml. The assay is based on the hydrolysis of double-stranded (ds) DNA (or nucleosomes) in agarose. The specificity of the reaction for DNase I was established by showing that either EDTA in the reaction buffer or G-actin abolished DNase activity. Being a functional assay, RED has advantages over radioimmunoassay (RIA) or ELISA, since antigenic assays may also measure complexes of DNase with actin. This method was used to measure DNase activity in the sera and urine of lupus-prone mice (NZB/NZW F1 hybrids, aged 4-6 weeks). Serum DNase activity in these mice was significantly lower (mean 9 ng/ml) than in control, normal mice of the same age and sex (mean 37 ng/ml). Concentration of DNase in the urine of 4-6-week-old female NZB/NZW F1 hybrids (24 ng/ml) was significantly lower then in control mice (521 ng/ml). The RED method was used to measure the concentration of actin as the DNase inhibitor in serum. G-actin in the presence of ATP binds DNase and inhibits its nucleolytic activity. Since ATP is necessary for the actin inhibition of DNase I, this shows that there is actin as well as DNase I in the serum. Actin is not only ATP-dependent, but also heat-labile. Heating the sera for 10 min at 50 degrees C increases DNase activity. This is an alternative method for measuring the concentration of actin in the serum. An almost identical estimate of actin concentration in sera of normal mice was found from the difference of DNase activity in the presence or absence of ATP (mean actin concentration = 21 ng/ml) or from the difference of DNase activity in heated and non-heated serum (mean actin concentration 18 ng/ml). We were not able to demonstrate DNase inhibitors in the urine of either control or NZB/W F1 hybrid mice.
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PMID:Measurement of deoxyribonuclease I (DNase) in the serum and urine of systemic lupus erythematosus (SLE)-prone NZB/NZW mice by a new radial enzyme diffusion assay. 915 89

The various phospholipid classes that comprise mammalian cell membranes are distributed over both leaflets of the bilayer in a non-random fashion. While a specific and ATP-dependent transporter is responsible for rapid inward movement of aminophospholipids, its inhibition does not lead to spontaneous redistribution of lipids. Conditions of cellular activation which are accompanied with increased levels of intracellular Ca2+ may cause a collapse of lipid asymmetry by switching on an ATP-independently operating scramblase, which accelerates bidirectional movement of all phospholipid classes. The most prominent change in transmembrane lipid distribution is surface exposure of phosphatidylserine (PS), the more so since conditions which activate scramblase in most if not all cases lead to inhibition of aminophospholipid translocase activity, which will prevent PS from being pumped back to the inner leaflet of the membrane. Surface-exposed PS serves at least two important physiological functions: it promotes blood coagulation and offers a recognition signal for clearance by macrophages and other cells of the reticuloendothelial system. As such, PS exposure may form an important early event in the process of apoptosis to ensure rapid removal of these cells in order to avoid release of their inflammatory contents. Defective regulation of transbilayer lipid distribution may result in clinical manifestations such as in the Scott syndrome, a bleeding disorder caused by an impaired scramblase activity. Conversely, excessive PS exposure may lead to thrombosis or may explain formation of so-called antiphospholipid antibodies as occurring in patients with antiphospholipid syndrome.
Lupus 1998
PMID:Regulatory mechanisms of transmembrane phospholipid distributions and pathophysiological implications of transbilayer lipid scrambling. 981 89

Phosphorylation of complement component C3 by different protein kinases in vitro has been demonstrated to alter the functional properties of the protein. Extracellular phosphorylation mediated by activated platelets is a newly described mechanism by which the function of plasma proteins can be regulated. Upon activation of platelets a casein kinase is released concomitant with large amounts of ATP and Ca2+. These components are sufficient to phosphorylate proteins e.g., C3 extracellularly. In vivo, in patients with SLE, the phosphate content in plasma proteins, including C3 has been demonstrated to increase during exacerbation. The changes were linked to platelet activation by a covariation with the levels of beta-thromboglobulin. The purpose of this review is to summarise the findings in this field.
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PMID:Phosphorylation of plasma proteins with emphasis on complement component C3. 1040 76


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