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The Amyloid β‐Protein of Alzheimer's Disease Increases Acetylcholinesterase Expression by Increasing Intracellular Calcium in Embryonal Carcinoma P19 Cells
Author(s) -
Sberna Gian,
SáezValero Javier,
Beyreuther Konrad,
Masters Colin L.,
Small David H.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69031177.x
Subject(s) - acetylcholinesterase , intracellular , calcium , calcium in biology , alzheimer's disease , chemistry , p19 cell , embryonal carcinoma , microbiology and biotechnology , biology , medicine , disease , neuroscience , biochemistry , enzyme , gene , cellular differentiation , adult stem cell
One of the characteristic changes that occurs in Alzheimer's disease is the loss of acetylcholinesterase (AChE) from both cholinergic and noncholinergic neurons of the brain. However, AChE activity is increased around amyloid plaques. This increase in AChE may be of significance for therapeutic strategies using AChE inhibitors. The aim of this study was to examine the effect of amyloid β‐protein (Aβ), the major component of amyloid plaques, on AChE expression. Aβ peptides spanning residues 1–40 or 25–35 increased AChE activity in P19 embryonal carcinoma cells. A peptide containing a scrambled Aβ 25–35 sequence did not stimulate AChE expression. To examine the possibility that the increase in AChE expression was mediated by an influx of calcium through voltage‐dependent calcium channels (VDCCs), drugs acting on VDCCs were tested for their effects. Inhibitors of L‐type VDCCs (diltiazem, nifedipine, and verapamil), but not N‐ or P‐ or Q‐type VDCCs, resulted in a decrease in AChE expression. Agonists of L‐type VDCCs (maitotoxin and S (−)‐Bay K 8644) increased AChE expression. As L‐type VDCCs are known to be modulated by cyclic AMP‐dependent protein kinase, the effect of the adenylate cyclase activator forskolin was also examined. Forskolin stimulated AChE expression, an action that was blocked by the L‐type VDCC antagonist nifedipine. The Aβ 25–35 ‐induced increase in AChE expression was mediated by an L‐type VDCC, as the effect was also blocked by nifedipine. The results suggest that the increase in AChE expression around amyloid plaques could be due to a disturbance in calcium homeostasis involving the opening of L‐type VDCCs.