Beta-amyloid induced increase in choline flux across PC12 cell membranes.
Beta-amyloid peptide is the main constituent of senile plaques and is implicated in the pathogenesis of Alzheimer's disease. It has been shown to be both neurotoxic and neurotrophic in vivo, and its effects have been suggested to be mediated in part by alterations in membrane transport. In the present study, we investigated the effect of beta-amyloid (1-40) on choline transport in cultured PC12 cells. We found that exposure to 46 or 92 microM beta-amyloid (1-40) increased [14C]choline flux in PC12 cells in a concentration-dependent manner, whereas exposure to reverse sequence beta-amyloid (40-1) had no effect. If there is a similar effect in vivo, the increased beta-amyloid dependent permeability to choline could lead to depletion of cellular choline stores and could contribute to the selective vulnerability of cholinergic neurons in Alzheimer's disease.
Allen
D D
DD
Laboratory of Neurosciences, NIA, NIH, Bethesda, MD 20892, USA. dallen@cortex.ama.ttuhsc.edu
Galdzicki
Z
Z
Brining
S K
SK
Fukuyama
R
R
Rapoport
S I
SI
Smith
Q R
QR
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002794:Choline / Q000378:metabolism*; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D051381:Rats
D016229:Amyloid beta-Peptides; D002794:Choline