Expression of mutant amyloid precursor proteins induces apoptosis in PC12 cells.
The cause of neuronal loss in Alzheimer disease is unknown. We investigated the effects on survival of PC12 cells expressing A692G, E693Q, and V717F mutant amyloid precursor proteins (APP). Differentiated cells expressing mutant APPs exhibited somal shrinkage, followed by cell detachment from the plates. Increased levels of oligonucleosome-sized DNA ladders and TUNEL-positive nuclei were observed, and electron microscopy revealed extensive plasma membrane blebbing, margination of condensed chromatin, and well-preserved organelles in these transfectants. The levels of TUNEL-positive cells, analyzed by a flow-cytometric method, were increased by four- to sevenfold in mutant APP transfectants, but less than twofold in wild-type APP transfectants relative to untransfected cells. Our results provide evidence that expression of mutant APPs in differentiated PC12 cells induces cell death via an apoptotic pathway.
Zhao
B
B
Molecular Neurobiology Unit/LBC, National Institute on Aging, Baltimore, Maryland 21224, USA.
Chrest
F J
FJ
Horton
W E
WE
Sisodia
S S
SS
Kusiak
J W
JW
D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001710:Biotin; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D053938:DNA Fragmentation; D003856:Deoxyuracil Nucleotides; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D016296:Mutagenesis / Q000502:physiology; D016716:PC12 Cells / Q000737:chemistry / Q000166:cytology* / Q000648:ultrastructure; D010641:Phenotype; D016133:Polymerase Chain Reaction; D051381:Rats; D013194:Staining and Labeling; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D003856:Deoxyuracil Nucleotides; D001710:Biotin