Proteins immunologically related to erythrocyte anion transporter band 3 are altered in brain areas affected by Alzheimer's disease

Bosman, G.J.C.G.M.; Workum, F. P. A. van; Renkawek, K; Kalmthout, P.J.C. Van; Bartholomeus, I.G.P.; Grip, W.J. de

doi:10.1007/bf00369447

Cited by 13 publications

(6 citation statements)

References 29 publications

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“…9). 14,64,78,102,103 One of these, an antibody to band 3 synthetic peptide pep-COOH, detected a triplet in the 60-70 kDa range in brains from patients with AD but not from age-matched controls (FIGS. 10A and 10B).…”

Section: Senescent Cell Antigen and Anti-band 3 Antibodies In Diseasesmentioning

confidence: 99%

Immunoregulation of Cellular Life Span

Kay

2005

Annals of the New York Academy of Sciences

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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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Section: Senescent Cell Antigen and Anti-band 3 Antibodies In Diseasesmentioning

confidence: 99%

Immunoregulation of Cellular Life Span

Kay

2005

Annals of the New York Academy of Sciences

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“…The fundamental principle by which lipid rafts carry out their functions is the separation or concentration of specific membrane proteins and lipids in membrane microdomains. Lipid rafts appear to be coupled to the dynamics of the actin cytoskeleton, especially through the major membrane-spanning protein known as the anion-exchanger protein (Bosman et al, 1993). Anionexchange (AE) proteins were recently identified as being clustered together in the hallmark plaques and tangles of AD patients' brains, indicating their possible role in toxic amyloid propagation (Xia et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Anionexchange (AE) proteins were recently identified as being clustered together in the hallmark plaques and tangles of AD patients' brains, indicating their possible role in toxic amyloid propagation (Xia et al, 2003). AE proteins (AE1, AE2, and AE 0) are members of a family related to band-3, a protein responsible for chloride/bicarbonate exchange and regulation of cell shape and are involved in generation of the senescent cell antigen, an antigen that facilitates the recognition and removal of old cells by the immune system (Bosman et al, 1993). Recently, it has been observed that Ab(25-35) inhibits the anion-exchange protein function, thereby elevating the intracellular chloride concentration of neurons (Yagyu, 2001).…”

Section: Introductionmentioning

confidence: 99%

Assemblages of prion fragments: novel model systems for understanding amyloid toxicity

Satheeshkumar

Jayaraman

Rajadas

2004

Journal of Structural Biology

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“…We have not found significant quantitative or qualitative differences in AE expression at the protein level when comparing immunoblots of Alzheimer and control brain tissues ( fig. 2, see also [30] have been reported with an antiserum against a peptide consisting of amino acids 812-827 of AE1 [45]. This antiserum also stained amy loid plaques, as did the antibody against a peptide in the fourth extracellular loop of AE1 ( fig.…”

Section: Resultsmentioning

confidence: 58%

“…In Alzheimer's disease-affected brain ar eas, some anti-AEl antisera show an in creased immunoreactivity especially in large pyramidal cells with a degenerative morphol ogy that do not (yet) contain mature neurofi brillary tangles [30,45]. An increased immu noreactivity, both in the number of reactive cells and in the reactivity per cell, is observed especially with antibodies against epitopes of the membrane domain of AE1 ( fig.…”

Section: Resultsmentioning

confidence: 98%

Involvement of Neuronal Anion Exchange Proteins in Cell Death in Alzheimer's Disease

Bosman¹,

Renkawek

Workum

et al. 1997

Gerontology

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Anion exchange (AE) proteins are present in human neurons in the brain. Immunohistochemical data indicate that their apparent expression level increases with age, and especially with degeneration in Alzheimer’s disease-affected brain areas. The increase in immunoreactivity is probably caused by changes in AE structure that lead to an increased accessibility of hitherto hidden epitopes. These epitopes correspond to regions in the membrane domain that are involved in generation of senescent cell-specific antigen from AE1 in aging erythrocytes. Elucidation of the molecular nature of these changes and the underlying mechanisms, will lead to insight in the processes that govern aging- and degeneration-associated perturbation of membrane integrity. AE-mediated chloride/bicarbonate exchange is a major component in the regulation of intracellular pH. The functional consequences of changes in AE structure may range from acidosis, disturbance of cytoskel-eton integrity, and untimely or impaired recognition of cells by components of the immune system, such as microglia. A molecular and physiological description of these changes will establish AE proteins as valuable tools in elucidating the processes of normal aging, and the disturbances in aging-related diseases such as Alzheimer’s disease.

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Proteins immunologically related to erythrocyte anion transporter band 3 are altered in brain areas affected by Alzheimer's disease

Cited by 13 publications

References 29 publications

Immunoregulation of Cellular Life Span

Immunoregulation of Cellular Life Span

Assemblages of prion fragments: novel model systems for understanding amyloid toxicity

Involvement of Neuronal Anion Exchange Proteins in Cell Death in Alzheimer's Disease

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