Amyloid-beta increases acetylcholinesterase expression in neuroblastoma cells by reducing enzyme degradation
Article first published online: 4 FEB 2004
Journal of Neurochemistry
Volume 86, Issue 2, pages 470–478, July 2003
How to Cite
Hu, W., Gray, N. W. and Brimijoin, S. (2003), Amyloid-beta increases acetylcholinesterase expression in neuroblastoma cells by reducing enzyme degradation. Journal of Neurochemistry, 86: 470–478. doi: 10.1046/j.1471-4159.2003.01855.x
- Issue published online: 4 FEB 2004
- Article first published online: 4 FEB 2004
- Received January 1, 2003; revised manuscript received April 3, 2003; accepted April 15, 2003.
- Alzheimer's disease;
- muscarinic receptors;
- protein turnover
Amyloid-beta (Aβ) is the principal protein constituent of ‘senile plaques’ and is a suspected mediator in Alzheimer's disease (AD). Senile plaques also contain acetylcholinesterase (AChE; EC 220.127.116.11), which may have a role in promoting Αβ-toxicity. We have found that Αβ can affect AChE expression in a neuron-like line, the N1E.115 neuroblastoma cell. When 1 µmΑβ 1–42 or 25–35 was added for 24 h to differentiating N1E.115 in culture, AChE activity increased 30–40% in adherent cells, and 100% or more in nonadherent cells. The changes in both tetrameric (G4) and monomeric (G1) AChE forms were comparable. Turnover studies indicated that the elevation of AChE activity reflected slowed AChE degradation rather than accelerated synthesis. With a similar time course, Αβ also increased the quantity of muscarinic receptors on the plasma membrane. Immunocytochemistry for a lysosomal membrane protein (LAMP-1) indicated no change in abundance or localization of lysosomes in treated cells. But decreased labeling by pH-sensitive fluorescent dye pointed to an impairment of lysosomal acidification. We consider that the alteration of AChE expression after Αβ-exposure could reflect lysosomal dysfunction, and might itself enhance Αβ-toxicity.