Pathogenic amyloid beta-protein induces apoptosis in cultured human cerebrovascular smooth muscle cells.
The amyloid beta-protein (A beta) pathologically accumulates in cerebral vascular and senile plaque deposits in the brains of patients with Alzheimer's disease (AD) and related disorders including hereditary cerebral hemorrhage with amyloidosis Dutch type (HCHWA-D). The cerebrovascular deposits are accompanied by degeneration and eventual loss of smooth muscle cells in cerebral vessel wall. Similarly, we have shown that pathogenic forms of A beta cause cell death in cultured human cerebrovascular smooth muscle (HCSM) cells in vitro. Here we show that pathogenic A beta induces a number of structural changes in HCSM cells including shrinkage of cell bodies, retraction 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 nuclear DNA, proteolytic breakdown of smooth muscle cell a actin, and proteolytic activation of the proteinase caspase 3. Together, these characteristics are consistent with an apoptotic mechanism of cell death in HCSM cells in response to pathogenic A beta.
Davis
J
J
Department of Medicine, State University of New York, Stony Brook 11794-8153, USA.
Cribbs
D H
DH
Cotman
C W
CW
Van Nostrand
W E
WE
D000199:Actins / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000098:blood supply*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D006868:Hydrolysis; D020287:In Situ Nick-End Labeling; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000502:physiology*
D000199:Actins; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases