Mmb. Kay et al., POSTTRANSLATIONAL MODIFICATIONS OF BRAIN AND ERYTHROCYTE BAND-3 DURING AGING AND DISEASE, Cellular and molecular biology, 42(7), 1996, pp. 919-944
Band 3 performs the same structural and functional activities in adult
brain as it does in erythrocytes. It ages as cells and tissues age Ou
r studies, to date, indicate that the anion transport ability of band
3 decreases in brains and lymphocytes from old mice. This decreased tr
ansport ability precedes obvious structural changes, such as band 3 de
gradation and generation of SCA and is the earliest change thus far de
tected in band 3. The following changes occur in lymphocytes, erythroc
ytes and brain band 3 with aging: 1) a decreased efficiency of anion t
ransport (decreased V-max) in spite of an increase in number of anion
binding sites (increased K-m, 2) a decreased glucose transport, 3) P-3
2 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 auto
antibodies in situ. The latter three findings indicate that posttransl
ational changes occur. In addition, the anion transporter, band 3, und
ergoes an as yet undefined change that results in binding of ''980'' a
ntibodies to aged band 3. Posttranslational changes in AD include decr
eased brain and RBC phosphorylation of a M(r) approximate to 135, 113
and 45 kDa band 3 polypeptides due to the phosphorylation site being a
lready 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 manife
sted in the brain because neurons accumulate damage throughout the lif
etime 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 protei
ns and functions.