Mapping of senescent cell antigen on brain anion exchanger protein (AE) isoforms using HPLC and fast atom bombardment ionization mass spectrometry (FAB-MS)

✍ Scribed by Marguerite M. Kay; Joseph Goodman

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 148 KB
• Volume: 17
• Category: Article
• ISSN: 0952-3499
• DOI: 10.1002/jmr.651

✦ Synopsis

Abstract

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. Copyright © 2003 John Wiley & Sons, Ltd.