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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteins are important constituents of the red blood cell plasma membrane. Several important breakthroughs have occurred in their analysis over the past few years. SDS-polyacrylamide gel electrophoresis lead to the separation of the major proteins and glycoproteins. Location of most of these proteins -- either on the external, the internal or both surfaces of the membrane -- was determined. The strenght of the binding of the protein to the membrane was established. Hydrophobicity of membrane proteins has so far hindered their purification. However, the major glycoprotein (glycophorin A) was isolated and recently sequenced. The description of several membrane-associated enzyme activities has been followed by some understanding of their specific role in the red blood cell physiology. Abnormalities of glycoproteins, Ca2+-ATPase and of membrane protein phosphorylation have been reported under various conditions: sickle cell disease, hereditary spherocytoses, progressive muscular dystrophy.
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PMID:[Erythrocyte membrane proteins]. 14 51

Twelve patients suffering from sickle cell anaemia (Hb less than 75 g/l) with SS-haemoglobin were studied with special regard to Band 3-protein content in their erythrocyte membranes on SDS-PAGE. They were compared in this respect with 7 asymptomatic individuals with AS-haemoglobin and 10 healthy controls with the ordinary adult haemoglobin. A heterogeneity in Band 3-protein content was evident among the 12 patients. Six of them belonged to a low content group while the other 6 belonged to a high content group comparable with the asymptomatic subjects and the controls. No simple relationship seemed to exist between Band 3-protein reduction and the clinical presentation.
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PMID:Reduction in band 3 protein of red cells in sickle cell anaemia. 189 60

Calpain, a calcium-dependent, neutral cysteine-protease was purified from the erythrocyte cytosol of subjects having essential hypertension (HTN), sickle cell anaemia, (SCA), or kwashiorkor (KWA). Identical electrophoretic mobility on SDS-polyacrylamide gradient gel, sensitivity to micromolar amounts of Ca2+, absolute requirement for a reducing environment and a high susceptibility to inhibition by leupeptin and thiol-group modifying reagents confirm that calpain preparations from these erythrocytes are equivalent to calpain I. Whereas the extent of calpain activation of erythrocyte membrane Ca2(+)-pumping ATPase of normal subjects was almost equal to that due to calmodulin, calpain activation of the HTN and SCA pump was greater than activation by calmodulin. Like in normal membranes, exogenous calmodulin protected the Ca2(+)-pumping ATPase of these erythrocytes against calpainization; the degree of protection by calmodulin is least in SCA and HTN. Electrophoretic separation of erythrocyte membranes and the purified Ca2(+)-pumping ATPase of HTN, SCA and KWA subjects does not indicate the presence of fragments resulting from the proteolytic action of calpain.
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PMID:Comparative action of calpain on erythrocyte Ca2(+)-pumping ATPase in sickle cell anaemia, essential hypertension and kwashiorkor. 214 87

Using ultrafiltration and SDS-PAGE, abnormal urinary protein excretion was found in 25.4% of 189 persons with sickle cell disease and trait, but none of 72 controls. Based upon molecular weight of urinary proteins, underlying renal lesions were classified as glomerular, tubular, or both. Altered protein excretion appeared at an early age, was more abnormal in older subjects, and was related to the severity of sickle cell disease (SS greater than SC = S/beta Thal greater than AS). Since none of the subjects had yet developed clinically significant renal disease, SDS-PAGE may permit early detection of patients who require careful follow-up or aggressive therapy.
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PMID:Proteinuria in sickle cell trait and disease: an electrophoretic analysis. 275 78

Phosphorylation of erythrocyte membrane proteins was determined in patients with homozygous sickle cell disease. After incubation of ghosts with gamma-32P ATP, proteins were submitted to SDS-polyacrylamide gel electrophoresis. Three salient features appeared: (i) a decreased phosphorylation of spectrin bands; (ii) a significantly increased phosphorylation (P less than 0.001) of bands 4(5) and 4(8) in the absence of cAMP and (iii) a significantly increased phosphorylation (P less than 0.001) of bands 7 and 8, both in the absence and the presence of cAMP. Studies on reticulocyte rich blood showed that the first change appeared to be specifically related to the disease, whilst the second resulted from the rejuvenation of the red cell population. No definite conclusion could be drawn for the third alteration.
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PMID:Erythrocyte membrane phosphorylation in sickle cell disease. 629 28

Elevations in intracellular calcium increase the adsorption of a cytoplasmic protein to human red blood cell membrane. This protein migrates on SDS polyacrylamide gels at 23,000 daltons and has been called band 8. The association of this protein with the membrane is increased in sickle cell anemia. This protein is extracted from the membrane with EGTA, a calcium chelator. Enzymatic and immunological studies identify band 8 as a glutathione S-transferase.
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PMID:Calcium-dependent association of glutathione S-transferase with the human erythrocyte membrane. 641 Oct 89

Transmembrane glycoproteins in the red cell membrane traverse the plasma membrane, have their carbohydrate moieties on the extracellular surface, are sialyated (except for band 3) and are tethered to the membrane cytoskeleton proteins on the cytoplasmic surface. This linkage between the transmembrane proteins and the skeletal membrane proteins provides a two-way communication between the extracellular surface and the interior of the red cell; i.e., a transmembrane effect can be initiated from either side. These interactions are discussed in this review, including the example of sickle cell anemia in which the membrane bound hemoglobin may exert a transmembrane effect to change the conformation or distribution of transmembrane glycoproteins and and hence the extracellular surface receptors. This, in turn, may explain why sickle cells adhere to endothelium in vitro. Although the RBC transmembrane sialoglycoproteins may function in communication, regulation of cell shape, and adhesion, uncertainties exist regarding many of their functions. To study these sialoglycoproteins, we have developed a double staining technique (Dzandu et al., 1984) that differentially stains human RBC membrane sialoglycoproteins and asialoproteins in SDS-polyacrylamide gels. This should aid in elucidating the conformational structure and function of transmembrane glycoproteins.
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PMID:Identification and function of transmembrane glycoproteins--the red cell model. 651 39

We have tested the hypothesis that dense cell formation in sickle cell disease is associated with increased binding of calpromotin to the membrane, an event that occurs during the activation of calcium-dependent potassium transport. By SDS polyacrylamide gel electrophoresis, we found that sickle cell membranes contained more calpromotin than did normal membranes when stained with Coomassie brilliant blue or when transferred to nitrocellulose paper and immunostained with horseradish peroxidase. Also, the membranes from dense sickle cells contained significantly (P = 0.00055) higher levels of calpromotin, 2.62+/-1.59 microg/mg membrane protein, compared to light sickle cells, 1.40+/-0.70 microg/mg membrane protein, when measured by an enzyme-linked immunosorbent assay. The ratio of calpromotin associated with dense cell membranes to light cell membranes was significantly greater than 1.0 (P < 0.00005). Transmission electron micrographs of immunogold-labelled membranes supported the increase in calpromotin binding in dense sickle cell membranes. In addition, the immunogold probe demonstrated clustering, which was not observed in light sickle cell membranes nor in normal membranes. Finally, we incubated HbSS cells in vitro using a repetitive deoxygenation/ reoxygenation procedure to produce dense cells and then measured the levels of calpromotin associated with their membranes. As expected, the levels of calpromotin bound to the membrane doubled during the procedure relative to the basal levels at the beginning of the incubation. The correlation coefficient, calculated between the increase in dense cell formation and the increase in calpromotin associated with the membrane, was statistically significant (P = 0.038). The results demonstrate that an increase in calpromotin binding to the membrane is associated with dense cell formation presumably through the activation of the calcium-dependent potassium channel.
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PMID:Calpromotin, a cytoplasmic protein, is associated with the formation of dense cells in sickle cell anemia. 932 51

SCD (stearoyl-CoA desaturase) catalyses the conversion of saturated fatty acids into mono-unsaturated fatty acids, a critical step involved in lipid metabolism and various other biological functions. In the present study, we report the identification and characterization of a human gene that encodes a novel SCD enzyme (hSCD2). The hSCD2 gene codes for a 37.5-kDa protein that shares 61% and 57% sequence identity with the human SCD1 and mouse SCD2 enzymes respectively. The recombinant hSCD2 enzyme expressed in mammalian and Sf9 insect cells efficiently catalysed desaturation of both stearoyl- and palmitoyl-CoAs to the corresponding mono-unsaturated fatty acids. In comparison with the hSCD1 gene that is predominantly expressed in liver, hSCD2 is most abundantly expressed in pancreas and brain. Additionally, hSCD2 transcripts from adult and foetal tissues exhibit different sizes because of alternative splicing in the non-coding region, suggesting that hSCD2 expression is developmentally regulated. The recombinant human SCD2 and SCD1 transiently expressed in COS-7 cells exhibited as oligomeric proteins that consist of homodimers and oligomers when resolved by SDS/PAGE. The complex formation was independent of SCD protein expression levels, as supported by a relatively constant ratio of the level of dimers and oligomers to that of the monomers from COS-7 cells transiently transfected with different amounts of SCD expression vectors. Furthermore, treatment of intact COS-7 cells with a cross-linking reagent resulted in dose-dependent increases in the levels of SCD protein and activity, suggesting that oligomerization may play an important role in regulating the stability of SCD enzymes.
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PMID:Characterization of human SCD2, an oligomeric desaturase with improved stability and enzyme activity by cross-linking in intact cells. 1561 69

Children with sickle cell anemia (SCA) frequently have short stature. We propose that alterations in the IGF-I axis are involved in their growth failure. We investigated the IGF-I axis in children with SCA and height below the 25th percentile (n = 15) and compared it with that of children with SCA and height above the 50th percentile (n = 7). IGF-I and IGFBP-3 levels were assessed by RIA. IGFBP-3 proteolysis was assessed by a protease activity assay and by Western immunoblots. IGF-I and IGFBP-3 SDS were low for both groups. In the short statured patients, IGF-I SDS correlated with height velocity SDS (p = 0.018). IGFBP-3 SDS, when corrected for bone age, decreased with age (p = 0.0054). IGFBP-3 was proteolyzed in both groups although the short statured patients had lower levels of absolute intact IGFBP-3 when compared with the normally growing group (p = 0.028). We demonstrated that children with SCA have abnormalities in the IGF-I axis, which worsen with age.
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PMID:Short stature in children with sickle cell anemia correlates with alterations in the IGF-I axis. 1739 38


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