Induction of acetylcholinesterase expression during apoptosis in various cell types

Abstract

Acetylcholinesterase (AChE) plays a key role in terminating neurotransmission at cholinergic synapses. AChE is also found in tissues devoid of cholinergic responses, indicating potential functions beyond neurotransmission. It has been suggested that AChE may participate in development, differentiation, and pathogenic processes such as Alzheimer's disease and tumorigenesis. We examined AChE expression in a number of cell lines upon induction of apoptosis by various stimuli. AChE is induced in all apoptotic cells examined as determined by cytochemical staining, immunological analysis, affinity chromatography purification, and molecular cloning. The AChE protein was found in the cytoplasm at the initiation of apoptosis and then in the nucleus or apoptotic bodies upon commitment to cell death. Sequence analysis revealed that AChE expressed in apoptotic cells is identical to the synapse type AChE. Pharmacological inhibitors of AChE prevented apoptosis. Furthermore, blocking the expression of AChE with antisense inhibited apoptosis. Therefore, our studies demonstrate that AChE is potentially a marker and a regulator of apoptosis.

Caspases shutdown nonsense-mediated mRNA decay during apoptosis

“…However, this contribution to apoptosis appears to be modest and is likely due to the wide spectrum of caspase targets that influence apoptosis. [3][4][5] Further investigations will be necessary to elucidate the mechanism underlying the induction of apoptosis by these UPF cleavage fragments, to identify the proteins that bind these fragments and in particular the highly conserved N-terminal UPF1 fragment for which there is, as yet, no clear function. With respect to UPF2, specific functions have not been correlated with the different regions of UPF2 other than the interaction domain in the C-terminal region with UPF1 and SMG1.…”

“…1 Cell death can occur via programed processes such as apoptosis, autophagy, necrosis (a more passive process) or necroptosis (a type of programed necrosis). 2 During apoptosis, specific gene networks and proteincleavage programs are activated sending the cells on a death spiral [3][4][5] through a family of cysteine-aspartate proteases (caspases). 6 Caspases are classified by their role in the apoptotic pathway, into (i) initiator caspases (such as caspases2, 8, 9 and 10) or (ii) effector caspases (such as caspases3, 6 or 7).…”

Differential localization of acetylcholinesterase in neuronal and non‐neuronal cells

“…AChE expression is not restricted to cholinergic neurons and hematopoietic cells. AChE has been shown to be expressed in osteoblasts, vascular endothelial cells, leukocytes, and to be induced in various cell lines undergoing apoptosis [Lan et al, 1996;Genever et al, 1999;Kirkpatrick et al, 2001;Zhang et al, 2002], and is typically associated with catalytic activity.…”

“…The Ellman assay is sensitive, rapid, and capable of measuring very low amounts of AChE catalytic activity. Neuronal cell lines and tissues are routinely assayed for ACh hydrolysis activity by the Ellman assay, but generally, tissue and cell lines that show negligible activity are considered negative for AChE protein expression [Kronman et al, 1992;Kris et al, 1994;Zhang et al, 2002].…”

Sequentially Programmable and Cellularly Selective Assembly of Fluorescent Polymerized Vesicles for Monitoring Cell Apoptosis

“…Accompanying with the apoptosis process, cholinesterase is overexpressed and transfers from cytoplasm to cell nucleus 56. So far, assays for caspases have received considerable attention for apoptosis imaging;18, 57 however, developing cholinesterase assay principles for apoptosis imaging is still on demand.…”