Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of carbamylation and frozen storage on the autologous 51Cr survival and metabolic features of sickle erythrocytes (S-RBCs) were determined. Red cells from four patients with sickle hemoglobinopathies were treated with 50 mM sodium cyanate for 2 hr (37 degrees C), glycerolized and frozen (-80 degrees C) for 62-153 days. The mean in vitro loss of S-RBCs from the combination of cyanate treatment and cryopreservation was 23.6% ( +/- 3.5 SD). The 2,3-diphosphoglycerate content of the thawed cells did not change significantly. However, ATP levels decreased to about 50% of the corresponding values in fresh, untreated S-RBCs. Despite this decrease in ATP, the mean intravascular survival of the frozen cyanated cells nearly doubled. At the high concentration of cyanate used, the oxygen affinity of S-RBCs increased markedly: Their mean P50 was 13.1 mm Hg ( +/- 1.9SD). The gelation of HbS at zero pO2 was also markedly inhibited in the one sample of cyanate-treated S-RBCs examined. Clinical studies to determine the efficacy of autologous transfusions with extensively carbamylated, cryopreserved S-RBCs should be considered.
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PMID:Autologous survival of cyanate-treated cryopreserved sickle erythrocytes. 395 59

The authors have studied the interactions of intact hemoglobin mixtures of HbE and HbA, with the major erythroid membrane skeletal protein, spectrin and tailor-made phospholipids membranes containing aminophospholipids to understand the role of spectrin and phospholipids of erythrocytes in the overall pathophysiology of the hemoglobin disorders. Hemoglobin mixtures were isolated and purified from the peripheral blood samples of HbE carriers and different HbEbeta thalassemia patients, taken for diagnosis. Spectrin binding was studied by fluorescence and oxidative crosslinking, by SDS-PAGE. Membrane perturbation experiments were carried out to study the leakage of the self-quenching fluorophore, carboxyfluorescein, entrapped in the phospholipid vesicles. Hemoglobin mixtures with elevated levels of HbE showed stronger interactions with spectrin reflected in the decrease in binding dissociation constant from 17 to 5 muM upon increase in HbE% from about 30 to 90% in the hemolysates. The yield of the spectrin crosslinked complexes of such hemoglobin mixtures also increased with increase in HbE levels. Presence of ATP/Mg and DPG were found to decrease the overall yield of such complexes and the binding affinity of hemoglobins to spectrin. HbE rich hemolysates also induced greater leakage of entrapped carboxyfluorescein (CF) from phospholipid membranes containing aminophospholipids. Results from this study indicate the roles of skeletal proteins and aminophospholipids, particularly under oxidative stress conditions to be important in the premature destruction of erythrocytes in hemoglobin disorders, e.g. HbEbeta-thalassaemia.
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PMID:Oxidative crosslinking, spectrin and membrane interactions of hemoglobin mixtures in HbEbeta-thalassemia. 1905 66

The asymmetric distribution of the amino-containing phospholipids, phosphatidyl-serine (PS) and phosphatidyl-ethanolamine (PE), across the two leaflets of red blood cell (RBC) membrane is essential to the function and survival of the cell. PS and PE are sequestered in the inner leaflet by an ATP-dependent transport activity of a membrane protein known as the RBC flippase that specifically moves amino-phospholipids from the outer to the inner leaflet. The enucleated RBC lacks the means to replace damaged enzymes and inactivation of the flippase can lead to the unwarranted exposure of PS on the cell surface. Loss in the ability to maintain phospholipid asymmetry is exacerbated in RBC disorders and PS-exposing RBCs present in the circulation play a significant role in the pathology of hemoglobinopathies. We identified the Atp8a1 protein, a member of the family of the P(4)-type ATPases, as a RBC flippase candidate. Atp8a1 is expressed in RBC precursors and is present in the membrane of mature red cells. The flippase activity of the protein was established in purified secretory vesicles of Saccharomyces cerevisiae. ATPase activity was stimulated by PS and PE. In addition, Atp8a1 can move PS molecules across the leaflets of the vesicle membrane in presence of ATP.
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PMID:ATP8A1 activity and phosphatidylserine transbilayer movement. 2022 45

Sickle cell anemia (SCA) is a hemoglobinopathy characterized by hemolysis and vaso-occlusions caused by rigidly distorted red blood cells. Sickle cell crisis is associated with extracellular release of nucleotides and platelets, which are critical mediators of hemostasis participating actively in purinergic thromboregulatory enzymes system.This study aimed to investigate the activities of purinergic system ecto-enzymes present on the platelet surface as well as CD39 and CD73 expressions on platelets of SCA treated patients. Fifteen SCA treated patients and 30 health subjects (control group) were selected. Ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), ecto-5'-nucleotidase (E-5'-NT) and ecto-adenosine deaminase (E-ADA) activities were measured in platelets isolated from these individuals. Results demonstrated an increase of 41 % in the E-NTPDase for ATP hydrolysis, 52% for ADP hydrolysis and 60 % in the E-ADA activity in SCA patients (P<0.05); however, a two folds decrease in the CD39 expression in platelets was observed in the same group (P<0.01). The increased E-NTPDase activity could be a compensatory mechanism associated with the low expression of CD39 in platelets. Besides, alteration of these enzymes activities suggests that the purinergic system could be involved in the thromboregulatory process in SCA patients.
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PMID:Altered E-NTPDase/E-ADA activities and CD39 expression in platelets of sickle cell anemia patients. 2704 34

This study examined particularly relevant redox pathways such as glycolysis, pentose phosphate pathway (PPP), metHb reductase and nucleotide metabolism, in order to better address how sickle cells deal with redox metabolism disruption. We also investigated the generation of specific oxidative lesions, and the levels of an unexplored antioxidant that could act as a candidate biomarker for oxidative status in sickle cell anemia (SCA). We adopted rigorous exclusion criteria to obtain the studied groups, which were composed by 10 subjects without hemoglobinopathies and 10 SCA patients. We confirmed that sickle cells overwhelm the antioxidant defense system, leading to an impaired antioxidant capacity that significantly contributed to the increase in cholesterol oxidation (ChAld) and hemolysis. Among the antioxidants evaluated, ergothioneine levels decreased in SCA (two-fold). We found strong correlations of ergothioneine levels with other erythrocyte metabolism markers, suggesting its use as an antioxidant therapy alternative for SCA treatment. Moreover, we found higher activities of MetHb reductase, AChE, G6PDH, HXK, and LDH, as well as levels of NADPH, ATP and hypoxanthine in sickle cells. On this basis, we conclude that impaired antioxidant capacity leaves to a loss of glycolysis and PPP shifting mechanism control and further homeostasis rupture, contributing to a decreased lifespan of sickle cells.
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PMID:Impaired antioxidant capacity causes a disruption of metabolic homeostasis in sickle erythrocytes. 3116 55

Sickle cell anemia (SCA) is a genetic hemoglobinopathy associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes and increase intramuscular acidosis. These alterations have been already reported in the Townes mouse model of SCA but the corresponding changes in humans have not been documented. In the present study, we used 31-phosphorus magnetic resonance spectroscopy in order to investigate in vivo the metabolic changes induced by a moderate-intensity exercise in twelve SCA patients, eight sickle cell trait (SCT) carriers and twelve controls women. The rest - exercise - recovery protocol disclosed slight differences regarding PCr consumption and lactate accumulation between SCA patients and controls but these differences did not reach a statistical significance. On that basis, the in vivo metabolic changes associated with a moderate-intensity muscle exercise were slightly altered in SCA patients and SCT carriers but within a normal range. The present results strongly support the fact that a moderate-intensity exercise is safe and could be recommended in stable SCA patients and SCT subjects.
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PMID:In vivo muscle function and energetics in women with sickle cell anemia or trait: a 31P magnetic resonance spectroscopy study. 3330 Aug 56