Induction of acetylcholinesterase expression during apoptosis in various cell types.
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.
Zhang
X J
XJ
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, China. zhang-xj@sunm.shcnc.ac.cn
Yang
L
L
Zhao
Q
Q
Caen
J P
JP
He
H Y
HY
Jin
Q H
QH
Guo
L H
LH
Alemany
M
M
Zhang
L Y
LY
Shi
Y F
YF
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015415:Biomarkers; D002451:Cell Compartmentation / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D005057:Eukaryotic Cells / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D016375:Antisense Elements (Genetics); D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D020033:Protein Isoforms; D012333:RNA, Messenger; D000110:Acetylcholinesterase; D000109:Acetylcholine