Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specific regions of the human erythrocyte anion transport protein, AE 1 or band 3, have been identified as being adhesive in Plasmodium falciparum-infected-erythrocytes. In addition, synthetic peptides based on these sequences and murine monoclonal antibodies (Mabs) to these block cytoadherence/sequestration. These findings suggest the possibility that humans who are able to control P. falciparum infections may produce anti-adhesin (and thus anti-band 3) antibodies. To test this hypothesis, sera from individuals living in The Gambia and southern California were assayed for reactivity to decapeptides patterned on putative exofacial regions of the human anion transporter, band 3 protein. Sera from an area highly endemic for malaria, The Gambia, were found to have strong reactivity to well-defined regions of the band 3 protein (some of which contain the adhesin), whereas minimal reactivity was observed with sera from individuals living in a geographic area where malaria transmission is rare (California). Sera from The Gambia reacted strongly with residue blocks 534-560, 638-660, and 808-842. Gambian sera that reacted strongly with peptides patterned on band 3 failed to react with native band 3 on an immunoblot, but did react with fixed P. falciparum-infected erythrocytes. Using reactivity to decapeptides has allowed the determination of the epitopes of previously described murine MAbs that inhibit or promote cytoadherence; this reactivity with a specific region of a protein can be correlated with a specific effect on cytoadherence. A MAb (5H12) directed against amino acids 474-488 promoted cytoadherence, whereas those directed against amino acids 540-550 and 750-766 (Mabs 1C4 and 4A3, respectively) inhibited cytoadherence.
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PMID:Plasmodium falciparum: sera of individuals living in a malaria-endemic region recognize peptide motifs of the human erythrocyte anion transport protein. 753 97

South-east Asian ovalocytosis status was determined in 1629 individuals originating from 12 different geographical areas of Papua New Guinea, representing different ethnic groups and degrees of malaria endemicity. This was achieved by using polymerase chain reaction amplification to demonstrate a 27 base pair deletion in the erythrocyte band 3 (AE1) gene. By using this method, the prevalence of erythrocyte band 3 gene deletion was determined to range from zero in both the lowland inland area of Wosera, East Sepik Province and the highland region of Goroka, Eastern Highlands Province to 35% on the north coast of Madang Province. In general, the prevalence correlated well with altitude, being highest on the coast where malaria transmission is high, intermediate in the lowlands, and lowest in the non-malarious highlands. However, Wosera, a lowland area in the Sepik River Plains, which is hyperendemic for malaria, was an exception in that no ovalocytosis was detected. These results largely confirm the prevalence rates that have been reported in the past using microscopy. In keeping with the autosomal dominant mode of inheritance, the male:female ratio was 1.02 and no homozygote was detected, indicating that homozygosity for the ovalocytosis band 3 gene deletion is lethal.
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PMID:Occurrence of the erythrocyte band 3 (AE1) gene deletion in relation to malaria endemicity in Papua New Guinea. 875 56

Band 3 is the most abundant integral protein of the red blood cell membrane. It performs two critical biological functions: maintaining ionic homeostasis, by transporting Cl- and HCO3-ions, and providing mechanical stability to the erythroid membrane. Erythroid band 3 (AE1) is one of three anion exchangers that are encoded by separate genes. The AE1 gene is transcribed by two promoters: the upstream promoter produces erythroid band 3, whereas the downstream promoter initiates transcription of the band 3 isoform in kidney. To assess the biological consequences of band 3 deficiency, we have selectively inactivated erythroid but not kidney band 3 by gene targeting in mice. Although no death in utero occurred, the majority of homozygous mice die within two weeks after birth. The erythroid band 3 null mice show retarded growth, spherocytic red blood cell morphology and severe haemolytic anaemia. Remarkably, the band 3-/- red blood cells assembled normal membrane skeleton thus challenging the notion that the presence of band 3 is required for the stable biogenesis of membrane skeleton. The availability of band 3-/- mice offers a unique opportunity to investigate the role of erythroid band 3 in the regulation of membrane-skeletal interactions, anion transport and the invasion and growth of malaria parasite into red blood cells.
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PMID:Targeted disruption of the murine erythroid band 3 gene results in spherocytosis and severe haemolytic anaemia despite a normal membrane skeleton. 884 Dec 2

In response to swelling cells recover their volume by releasing ions (mainly K+, Cl-) and different organic solutes (e.g. taurine) via volume-sensitive pathways. Depending on the cause of swelling (net uptake of electrolytes or decrease in external osmolality) cells use specifically some of these pathways. Previous data indicate that the anion exchanger (AE1) is involved in the choice of the regulatory pattern the cells adopt. Molecular cloning and functional expression of AE1 from the trout erythrocyte shows that this anion exchanger can function as a channel mediating taurine fluxes. In the erythrocyte, the channel activation depends on the conditions as the cell is swollen: when swelling is caused by an accumulation of electrolytes (resulting in an increase of the intracellular ionic strength) the channel is not activated and the regulatory volume decrease occurs exclusively by a release of K and Cl via a KCl cotransporter. When swelling is caused by hypotonic shock (resulting in a decrease in intracellular ionic strength) the KCl cotransporter is then mainly inactivated or even silent; conversely the channel is activated and allows volume recovery by mediating the release of both taurine and probably K and Cl. The possibility that AEs function as volume-activated taurine channels in other cell types and as a malaria-induced channel in malaria-infected human red cells is considered.
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PMID:A role for the anion exchanger AE1 (band 3 protein) in cell volume regulation. 896 Jul 75

In response to swelling, cells recover their initial volume by releasing intracellular solutes via volume-sensitive pathways. There is increasing evidence that structurally dissimilar organic osmolytes (amino acids, polyols, methyl amines), which are lost from cells in response to swelling, share a single pathway having the characteristics of an anion channel. However, the molecular identity of this pathway remains to be established. It has been suggested that the erythrocyte anion exchanger (AE1) or some AE1-related proteins could be involved. A direct evaluation of this possibility has been made by comparing the functional properties of two AE1s when expressed in Xenopus laevis oocytes: tAE1 is from a fish erythrocyte which releases taurine when swollen, and mAE1 is from a mammalian erythrocyte which does not regulate its volume when swollen. While mAE1 performs exclusively Cl-/Cl- exchange, tAE1 behaves as a bifunctional protein with both anion exchange and Cl-/taurine channel functions. Construction of diverse tAE1/mAE1 chimaeras allows the identification of protein domains associated with this channel activity. Thus, some AE1 isoforms could act as a swelling-activated osmolyte channel, a result having a potentially important implication in malaria. This review also discusses the possibility that several different proteins might function as swelling-activated osmolyte channels.
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PMID:Association of the band 3 protein with a volume-activated, anion and amino acid channel: a molecular approach. 905 Feb 45

Glycophorin A is the major transmembrane sialoglycoprotein of red blood cells. It has been shown to contribute to the expression of the MN and Wright blood group antigens, to act as a receptor for the malaria parasite Plasmodium falciparum and Sendai virus, and along with the anion transporter, band 3, may contribute to the mechanical properties of the red blood cell membrane. Several lines of evidence suggest a close interaction between glycophorin A and band 3 during their biosynthesis. Recently, we have generated mice where the band 3 expression was completely eliminated by selective inactivation of the AE1 anion exchanger gene, thus allowing us to study the effect of band 3 on the expression of red blood cell membrane proteins. In this report, we show that the band 3 -/- red blood cells contain protein 4.1, adducin, dematin, p55, and glycophorin C. In contrast, the band 3 -/- red blood cells are completely devoid of glycophorin A (GPA), as assessed by Western blot and immunocytochemistry techniques, whereas the polymerase chain reaction (PCR) confirmed the presence of GPA mRNA. Pulse-label and pulse-chase experiments show that GPA is not incorporated in the membrane and is rapidly degraded in the cytoplasm. Based on these findings and other published evidence, we propose that band 3 plays a chaperone-like role, which is necessary for the recruitment of GPA to the red blood cell plasma membrane.
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PMID:Complete deficiency of glycophorin A in red blood cells from mice with targeted inactivation of the band 3 (AE1) gene. 949 Jul 2

This review discusses recent advances in our understanding of the structure, function and molecular genetics of the membrane domain of red cell anion exchanger, band 3 (AE1), and its role in red cell and kidney disease. A new model for the topology of band 3 has been proposed, which suggests the membrane domain has 12 membrane spans, rather than the 14 membrane spans of earlier models. The major difference between the models is in the topology of the region on the C-terminal side of membrane spans 1-7. Two dimensional crystals of the deglycosylated membrane domain of band 3 have yielded two and three dimensional projection maps of the membrane domain dimer at low resolution. The human band 3 gene has been completely sequenced and this has facilitated the study of natural band 3 mutations and their involvement in disease. About 20% of hereditary spherocytosis cases arise from heterozygosity for band 3 mutations, and result in the absence or decrease of the mutant protein in the red cell membrane. Several other natural band 3 mutations are known that appear to be clinically benign, but alter red cell phenotype or are associated with altered red cell blood group antigens. These include the mutant band 3 present in Southeast Asian ovalocytosis, a condition which provides protection against cerebral malaria in children. Familial distal renal tubular acidosis, a condition associated with kidney stones, has been shown to result from a novel group of band 3 mutations. The total absence of band 3 has been described in animals-occurring naturally in cattle and after targeted disruption in mice. Some of these severely anaemic animals survive, so band 3 is not strictly essential for life. Although the band 3-negative red cells were very unstable, they contained a normally-assembled red cell skeleton, suggesting that the bilayer of the normal red cell membrane is stabilized by band 3 interactions with membrane lipids, rather than by interactions with the spectrin skeleton.
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PMID:The structure and function of band 3 (AE1): recent developments (review). 949 67

The role of the erythrocyte anion exchanger, band 3 protein (AE1), in the adhesion of Plasmodium falciparum-infected erythrocytes to CD36 and thrombospondin (TSP) was studied. Two specific anion exchange inhibitors that bind covalently to different regions of the band 3 molecule affected cytoadherence in dissimilar ways. Modification of lysine 539 by diisothiocyanostilbene sulfonic acid (DIDS) resulted in a significant reduction in the adhesive properties of parasitized erythrocytes for CD36, but not TSP, whereas treatment with fluorescein-5-maleimide, which modifies lysine 430, was without effect on both TSP and CD36 binding. The adhesive properties of the DIDS binding region (DBR) was demonstrated by competition experiments using synthetic peptides and by direct interaction of such peptides with CD36 transfected CHO cells. The results suggest that host membrane proteins such as AE1 contribute to the adhesion of malaria-infected erythrocytes to CD36.
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PMID:Chemical modifications of band 3 protein affect the adhesion of Plasmodium falciparum-infected erythrocytes to CD36. 1547 2

Our current studies focus on the molecular changes induced by aging. During aging, changes in proteins occur that alter their function and render them immunogenic. These "neoantigens" are recognized by physiologic autoantibodies. Physiologic autoantibodies and their corresponding antigens offer therapeutic strategies for disease intervention through the innate immune response. Early studies done in the 1970s showed humans and animals to have physiologic antibodies that bind to a neoantigen called senescent cell antigen (SCA), which appears on senescent and damaged cells and initiates their removal by macrophages. These studies led to the discovery that oxidation can generate a new antigen in situ. Oxidation accelerated aging of red cells, generated SCA and IgG binding, and triggered removal of red cells by macrophages. Since then, a number of laboratories have found that oxidation can generate other neoantigens. For example, oxidized LDL (OxLDL) induces antibodies that can modify the natural progression of atherosclerosis. Apoptotic cells express oxidatively modified moieties on their surfaces that are involved in macrophage recognition and phagocytosis. Physiologic autoantibodies were used to isolate SCA from brain tissue. HPLC and fast atom bombardment ionization mass spectrometry (FAB-MS) of the isolated antigen suggested that the aging antigen is a subset of band 3, a family of proteins also called anion exchange proteins (AE1-3). FAB-MS results indicate that residues matching all three band 3 isoforms (AE1, AE2, and AE3) are detected in aging antigen fractions. Among the fragments identified with FAB-MS was a sequence corresponding to an aging epitope, human band 3 sequence LFKPPKYHPDVPYVKR, residue 812-830 in AE1; HHPDVTYVK, residue 1144-1152 in AE2; or HHPEQPYVTK, residue 1135-1144 in AE3. A residue that is close to that region was identified in mouse AE1 ASGPGAAAQIQEVK, residue 762-775. The potential for altering the natural progression of diseases using select peptide-defined epitopes within or overlapping the aging antigenic site (547-553 and 824-829) is discussed using the innate immune response to band 3 in malaria as an example.
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PMID:Immunoregulation of cellular life span. 1639 89

The anion-exchange protein 1 (AE1 or band 3) is involved in the erythrocyte invasion of the malaria parasite Plasmodium falciparum, the adhesion of infected erythrocytes to endothelial cells, and the regulation of acid-base homeostasis, which is a critical factor for human survival in severe malaria. A variant of the AE1 gene promoter 512 base pairs (bp) distant from the transcription start site and 5699 bp from the translation start codon (AE1(-5699T-->C)) has been shown to be highly frequent in a population from the Ashanti region, Ghana. In a matched-pair case-control study (736 pairs), children heterozygous for the mutation (AE1(-5699CT)) had an increased risk of severe malarial anemia (odds ratio [OR], 1.45 [95% confidence interval {CI}, 1.05-2.01]; P<.03). In children who developed this complication, carriers of the mutation AE1(-5699C) had a higher fatality rate than those with the genotype AE1(-5699TT) (relative risk, 7.1 [95% CI, 1.0-52.8]). Moreover, in children with cerebral malaria, AE1(-5699C) was positively associated with a distinctive metabolic acidosis (P<.002), and results of luciferase assays showed higher transcriptional activity of the AE1(-5699C) allele. These results demonstrate that the AE1 promoter allele might influence the infection phenotype and the risk of fatal outcome in children with severe malaria. In this regard, a crucial role of the AE1 protein in malaria is emphasized.
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PMID:Promoter polymorphism of the anion-exchange protein 1 associated with severe malarial anemia and fatality. 1696 Jul 83


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