Posttranslational modifications of brain and erythrocyte band 3 during aging and disease.
Band 3 performs the same structural and functional activities in adult brain as it does in erythrocytes. It ages as cells and tissues age Our studies, to date, indicate that the anion transport ability of band 3 decreases in brains and lymphocytes from old mice. This decreased transport ability precedes obvious structural changes, such as band 3 degradation and generation of SCA and is the earliest change thus far detected in band 3. The following changes occur in lymphocytes, erythrocytes and brain band 3 with aging: 1) a decreased efficiency of anion transport (decreased Vmax) in spite of an increase in number of anion binding sites (increased K(m)), 2) a decreased glucose transport, 3) 32P labeling in vitro, 4) an increased degradation to smaller fragments as detected by quantitative binding of antibodies to band 3 breakdown products and residue 812-830, and 5) a binding of physiologic IgG autoantibodies in situ. The latter three findings indicate that posttranslational changes occur. In addition, the anion transporter, band 3, undergoes an as yet undefined change that results in binding of "980" antibodies to aged band 3. Posttranslational changes in AD include decreased brain and RBC phosphorylation of a M(r) = 135, 113 and 45 kDa band 3 polypeptides due to the phosphorylation site being already occupied, increased degradation of band 3, alterations in band 3 recognized by antibodies, and decreased anion and glucose transport by blood cells. Band 3 in erythrocytes of AD patients has a different immunological identity from normal band 3 as evidenced by the binding of antibodies described in this study. AD may be preferentially manifested in the brain because neurons accumulate damage throughout the lifetime as they do not regenerate or undergo cell division. We suspect, and our data indicate, that the same mechanism(s) of AD occurs in all cells, but that the manifestations differ due to different cell proteins and functions.
Kay
M M
MM
Dept. of Microbiology and Immunology, Veterans Administration Research Service, University of Arizona College of Medicine, Tucson 85724-5049, USA.
Rapcsak
S Z
SZ
Bosman
G J
GJ
Goodman
J R
JR
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000097:blood / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational
D001457:Anion Exchange Protein 1, Erythrocyte; D000975:Antioxidants; D005947:Glucose