GSK3beta mediates the induced expression of synaptic acetylcholinesterase during apoptosis.
Besides its role in terminating acetylcholine-mediated neurotransmission, acetylcholinesterase (AChE) is found to be expressed and participate in the process of apoptosis in various cell types. However, the mechanisms underlying AChE up-regulation in neuronal cells remain elusive. Herein we demonstrated that glycogen synthase kinase-3beta (GSK3beta) mediates induced AChE-S expression during apoptosis. In this study, A23187 and thapsigargin (TG) were employed to induce apoptosis in neuroendocrine PC12 cells. The results showed that exposure of PC12 cells to A23187 and TG up-regulated AChE activity significantly. The same treatment also led to activation of GSK3beta. Two different inhibitors of GSK3beta (lithium and GSK3beta-specific inhibitor VIII) could block A23187- or TG-induced up-regulation of AChE activity, AChE-S mRNA level and protein expression. However, lithium could not inhibit the induction of AChE-R mRNA and protein under similar conditions. Taken together, our results show that GSK3beta is specifically involved in the induction of AChE-S expression in PC12 cells during apoptosis.
Jing
Peng
P
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
Jin
Qihuang
Q
Wu
Jun
J
Zhang
Xue-Jun
XJ
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007454:Iodides; D007476:Ionophores / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000201:enzymology*; D019284:Thapsigargin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D004791:Enzyme Inhibitors; D007454:Iodides; D007476:Ionophores; D012333:RNA, Messenger; D000001:Calcimycin; D019284:Thapsigargin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D000110:Acetylcholinesterase; D018021:Lithium Chloride