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Plasma Glycoprotein (plasma + glycoprotein)
Selected AbstractsStudy of mutations in Jordanian patients with haemophilia A: identification of five novel mutationsHAEMOPHILIA, Issue 1 2010A. AWIDI Summary., Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by mutations in the factor VIII gene (F8), which encodes factor VIII (FVIII) protein, a plasma glycoprotein, that plays an important role in the blood coagulation cascade. In the present study, our aim was to identify F8 gene mutations in HA patients from Jordan. One hundred and seventy-five HA patients from 42 unrelated families were included in this study. Among these patients, 117 (67%) had severe HA, 13 (7%) had moderate HA and 45 (26%) had mild HA. Severe patients were first tested for intron-22 inversion using long range polymerase chain reaction (PCR), then negative patients were tested for intron-1 inversion using PCR. Sequencing for the entire F8 gene was performed for all severe HA patients who were found negative for intron-22 and -1 inversions and it was also performed for moderate and mild HA patients. HA causative mutations were identified in all patients. Intron-22 and -1 inversions were detected in 52% and 2% of families respectively. Beside these two mutations, 19 different mutations were identified, which include 15 missense and four frameshift mutations. Five novel mutations were identified including one frameshift and four missense mutations. No large deletions or nonsense mutations were detected in patients who participated in this study. Only 17 patients with severe HA were found positive for FVIII inhibitors. The data presented will play an important role for genetic counselling and health care of HA patients in Jordan. [source] Haemopexin affects iron distribution and ferritin expression in mouse brainJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 10 2009Noemi Morello Abstract Haemopexin (Hx) is an acute phase plasma glycoprotein, mainly produced by the liver and released into plasma where it binds heme with high affinity and delivers it to the liver. This system provides protection against free heme-mediated oxidative stress, limits access by pathogens to heme and contributes to iron homeostasis by recycling heme iron. Hx protein has been found in the sciatic nerve, skeletal muscle, retina, brain and cerebrospinal fluid (CSF). Recently, a comparative proteomic analysis has shown an increase of Hx in CSF from patients with Alzheimer's disease, thus suggesting its involvement in heme detoxification in brain. Here, we report that Hx is synthesised in brain by the ventricular ependymal cells. To verify whether Hx is involved in heme scavenging in brain, and consequently, in the control of iron level, iron deposits and ferritin expression were analysed in cerebral regions known for iron accumulation. We show a twofold increase in the number of iron-loaded oligodendrocytes in the basal ganglia and thalamus of Hx-null mice compared to wild-type controls. Interestingly, there was no increase in H- and L-ferritin expression in these regions. This condition is common to several human neurological disorders such as Alzheimer's disease and Parkinson's disease in which iron loading is not associated with an adequate increase in ferritin expression. However, a strong reduction in the number of ferritin-positive cells was observed in the cerebral cortex of Hx-null animals. Consistent with increased iron deposits and inadequate ferritin expression, malondialdehyde level and Cu,Zn superoxide dismutase-1 expression were higher in the brain of Hx-null mice than in that of wild-type controls. These data demonstrate that Hx plays an important role in controlling iron distribution within brain, thus suggesting its involvement in iron-related neurodegenerative diseases. [source] ,2 -glycoprotein i is a cofactor for tissue plasminogen activator,mediated plasminogen activationARTHRITIS & RHEUMATISM, Issue 2 2009Chunya Bu Objective Regulation of the conversion of plasminogen to plasmin by tissue plasminogen activator (tPA) is critical in the control of fibrin deposition. While several plasminogen activators have been described, soluble plasma cofactors that stimulate fibrinolysis have not been characterized. The purpose of this study was to investigate the effects of ,2 -glycoprotein I (,2GPI), an abundant plasma glycoprotein, on tPA-mediated plasminogen activation. Methods The effect of ,2GPI on tPA-mediated activation of plasminogen was assessed using amidolytic assays, a fibrin gel, and plasma clots. Binding of ,2GPI to tPA and plasminogen was determined in parallel. The effects of IgG fractions and anti-,2GPI antibodies from patients with antiphospholipid syndrome (APS) on tPA-mediated plasminogen activation were also measured. Results Beta2 -glycoprotein I stimulated tPA-dependent plasminogen activation in the fluid phase and within a fibrin gel. The ,2GPI region responsible for stimulating tPA activity was shown to be at least partly contained within ,2GPI domain V. In addition, ,2GPI bound tPA with high affinity (Kd ,20 nM), stimulated tPA amidolytic activity, and caused an overall 20-fold increase in the catalytic efficiency (Kcat/Km) of tPA-mediated conversion of Glu-plasminogen to plasmin. Moreover, depletion of ,2GPI from plasma led to diminished rates of clot lysis, with restoration of normal lysis rates following ,2GPI repletion. Stimulation of tPA-mediated plasminogen activity by ,2GPI was inhibited by monoclonal anti-,2GPI antibodies as well as by anti-,2GPI antibodies from patients with APS. Conclusion These findings suggest that ,2GPI may be an endogenous regulator of fibrinolysis. Impairment of ,2GPI-stimulated fibrinolysis by anti-,2GPI antibodies may contribute to the development of thrombosis in patients with APS. [source] The heterogeneity of the glycosylation of alpha-1-acid glycoprotein between the sera and synovial fluid in rheumatoid arthritisBIOMEDICAL CHROMATOGRAPHY, Issue 4 2002Kevin D. Smith Alpha-1-acid glycoprotein (AGP) is a plasma glycoprotein produced by the liver that undergoes increased production and altered glycosylation in several physiological and pathological conditions including rheumatoid arthritis. To date, although present in the synovial fluid of rheumatoid arthritis patients, there has been no evidence for the separate extra-hepatic production of AGP. This study indicates that there could be a localized production of AGP in rheumatoid synovial fluid by demonstrating that the glycosylation patterns of AGP differed between the serum and synovial fluid in the same rheumatoid patient. Serum AGP was largely composed of fucosylated tri- and tetra-antennary oligosaccharide chains while the synovial fluid contained mainly bi-antennary chains that were fucosylated to a lesser extent. This structural heterogeneity of glycosylation resulted in functional diversity; serum but not synovial AGP is able to inhibit binding to the cell adhesion molecule E-selectin through expression of antigen sialyl Lewis X. Copyright © 2002 John Wiley & Sons, Ltd. [source] Translational Mini-Review Series on Complement Factor H: Genetics and disease associations of human complement factor HCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2008S. Rodríguez De Córdoba Summary Factor H is an abundant plasma glycoprotein that plays a critical role in the regulation of the complement system in plasma and in the protection of host cells and tissues from damage by complement activation. Several recent studies have described the association of genetic variations of the complement factor H gene (CFH) with atypical haemolytic uraemic syndrome (aHUS), age-related macular degeneration (AMD) and membranoproliferative glomerulonephritis (MPGN). This review summarizes our current knowledge of CFH genetics and examines the CFH genotype,phenotype correlations that are helping to understand the molecular basis underlying these renal and ocular pathologies. [source] | ||||||||||