Amyloid precursor protein fragment and acetylcholinesterase increase with cell confluence and differentiation in a neuronal cell line.
This study addresses the developmental regulation of amyloid precursor protein (APP) fragments comprising the amyloid-beta peptide (AP) and the amyloid-promoting factor acetylcholinesterase (AChE) in a mouse neuronal cell line (Neuro-2a). Results indicate that a 35-kDa amyloidogenic fragment of APP and the major molecular forms of AChE (G1 and G4) in Neuro-2a cells significantly increase with increasing levels of cell confluence. The foregoing molecules undergo further increases when neuroblastoma cells differentiate in the presence of dibutyryl cAMP. In contrast, a 17-kDa fragment of APP and butyrylcholinesterase were not affected by cell confluence or differentiation. These findings are the first to indicate that a selective Abeta-containing fragment of APP is subject to developmental regulation. Moreover, our data show that the 35-kDa fragment and AChE forms respond in parallel to the same developmental stimuli, i.e., cell confluence and differentiation. This points to the existence of a functional relationship between both molecules, a notion that is consistent with the potential role that has been ascribed to AChE in both APP processing and the formation of amyloid deposits in Alzheimer's brains.
Bronfman
F C
FC
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago.
Fernandez
H L
HL
Inestrosa
N C
NC
D000110:Acetylcholinesterase / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002091:Butyrylcholinesterase / Q000096:biosynthesis; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D016564:Amyloid beta-Protein Precursor; D002800:Cholinesterase Inhibitors; D010446:Peptide Fragments; D003994:Bucladesine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase