Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q8NB91 (FAB)
 3,573 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular recognition of senescent cells involves oxidation of a crucial membrane protein leading to generation of a neoantigen, called 'senescent cell antigen' (SCA), and binding of physiologic autoantibodies. These IgG autoantibodies trigger macrophage removal of the cell prior to its lysis at a time when anion transport has decreased but the membrane is still grossly intact. The neoantigen SCA is generated by oxidation of a major anion transport protein called band 3 or anion exchange protein. In this study, we use IgG physiologic autoantibodies from senescent red cells to isolate SCA from brain, and HPLC and fast atom bombardment ionization mass spectrometry (FAB-MS) to compare brain SCA to band 3. HPLC peptide maps of band 3 and SCA showed substantial homology, suggesting that SCA is a subset of band 3, and includes an estimated >/=45% of the band 3 molecule. FAB-MS results indicate that residues matching all three band 3 isoforms (AE1, AE2 and AE3) are detected in SCA fractions. These findings suggest that other isoforms of band 3 may undergo the same aging changes that AE1 on red blood cells undergoes to generate SCA. This provides confirmation that SCA is on non-erythroid cell types. Implications of these studies to the generation of neoantigens by oxidation and their recognition by autoantibodies to them are discussed.
 ...
PMID:Mapping of senescent cell antigen on brain anion exchanger protein (AE) isoforms using HPLC and fast atom bombardment ionization mass spectrometry (FAB-MS). 1487 35

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.
 ...
PMID:Immunoregulation of cellular life span. 1639 89