Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sickle cell erythrocytes exhibit reduced carboxyl methylation of membrane proteins compared to normal erythrocytes. This altered methylation in sickle membrane proteins is also observable when extracted membranes, both intact and alkali treated, were used as substrates for the homologous protein methylase II (S-adenosylmethionine:protein-carboxyl O-methyltransferase, EC. 2.1.1.24). However, when glycophorin A, one of the major methyl acceptors in both membranes, was extracted by lithium diiodosalicylate and used as the methyl acceptor, the proteins from both membranes were methylated equally, suggesting an involvement of membrane structure in membrane-bound protein methylation. Merocyanine 540 (MC-540), a fluorescent probe, was used to determine if the membranes differed in organization. Incubation of both normal and sickle erythrocytes membranes with MC-540 produced a marked increase in extrinsic fluorescence, reflecting a relatively nonpolar environment for the dye bound to the membranes. The fluorescence from sickle cell ghosts was only 87% as intense as that from normal ghosts, while the actual amount of MC-540 associated with sickle cell membranes was only 62% of normal. These data suggest that differences exist in the distribution of surface charges on these plasma membranes. These results are consistent with the hypothesis that abnormal levels of membrane protein methylation observed in sickle erythrocytes may be a result of abnormal membrane organization characteristic to sickle cell anemia.
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PMID:Abnormal membrane protein methylation and merocyanine 540 fluorescence in sickle erythrocyte membranes. 647 41

The methylation of erythrocyte membrane components in sickle cell anemia has been studied and found to differ considerably from that of normal erythrocytes. When sickle erythrocytes were incubated under physiological conditions (pH = 7.4, 37 degrees C) in the presence of L-[methyl-3H]methionine or S-adenosyl-L-[methyl-3H] methionine, a 50% decrease in the protein-carboxyl methylation was observed compared to the normal erythrocyte. This reduction in degree of methylation was reflected in all of the major methylated protein bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Since this methylation is catalyzed by the cytosolic protein methylase II (S-adenosylmethionine:protein-carboxyl O-methyltransferase, EC 2.1.1.24), the in vitro substrate capability of sickle erythrocyte ghosts and pH 11 treated ghosts were tested by incubation with purified protein methylase II and S-adenosyl-L-[methyl-14C]methionine. Both types of sickle cell ghost preparations showed the same 50% decrease in methylation as was seen in the intact cells. Since it was also shown that the protein methylase II and methyl acceptor membrane protein levels in the sickle erythrocytes are the same as the normal control, the data suggest that the observed reduced methylation may be due to an altered membrane conformation. The methylation of phospholipid was also studied and found to be decreased in sickle cell erythrocytes. However, this methylation was extremely minor in comparison to protein-carboxyl methylation which represents the bulk of the membrane methylation.
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PMID:Reduced erythrocyte membrane protein methylation in sickle cell anemia. 728 25