J. Davis et al., Pathogenic amyloid beta-protein induces apoptosis in cultured human cerebrovascular smooth muscle cells, AMYLOID, 6(3), 1999, pp. 157-164
Citations number
32
Categorie Soggetti
Medical Research General Topics
Journal title
AMYLOID-INTERNATIONAL JOURNAL OF EXPERIMENTAL AND CLINICAL INVESTIGATION
The amyloid beta-protein (A beta) pathologically accumulates in cerebral va
scular and senile plague deposits in the brains of patients with Alzheimer'
s disease (AD) and related dis. orders including hereditary cerebral hemorr
hage with amyloidosis Dutch type (HCMWA-D). The cerebrovascular deposits ar
e accompanied by degeneration and eventual loss of smooth muscle cells in c
erebral vessel wall. Similarly, we have shown that pathogenic forms of A be
ta cause cell death in cultured human cerebrovascular smooth muscle (HCSM)
cells in vitro. Here we show that pathogenic A beta induces a number of str
uctural changes in HCSM cells Including shrinkage of cell bodies, retractio
n of processes, disruption of the intracellular actin network, and nuclear
condensation and fragmentation. These changes were accompanied by a number
of biochemical alterations in the cells shown by in situ end labeling of nu
clear DNA, proteolytic breakdown of smooth muscle cell a actin, and proteol
ytic activation of the proteinase caspase 3. Together, these characteristic
s are consistent with an apoptotic mechanism of cell death in HCSM cells in
response to pathogenic A beta.