Regulation of acetylcholinesterase expression by calcium signaling during calcium ionophore A23187- and thapsigargin-induced apoptosis

Hui Zhu, Wei Gao, Hua Jiang, Qi Huang Jin, Yu Fang Shi, Karl W.K. Tsim, Xue Jun Zhang

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

We have recently reported that acetylcholinesterase expression was induced during apoptosis in various cell types. In the current study we provide evidence to suggest that the induction of acetylcholinesterase expression during apoptosis is regulated by the mobilization of intracellular Ca2+. During apoptosis, treatment of HeLa and MDA-MB-435s cells with the calcium ionophore A23187 resulted in a significant increase in acetylcholinesterase mRNA and protein levels. Chelation of intracellular Ca2+ by BAPTA-AM (1,2-bis-(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid-acetoxymethyl ester), an intracellular Ca2+ chelator, inhibited acetylcholinesterase expression. A23187 also enhanced the stability of acetylcholinesterase mRNA and increased the activity of acetylcholinesterase promoter, effects that were blocked by BAPTA-AM. Perturbations of cellular Ca2+ homeostasis by thapsigargin resulted in the increase of acetylcholinesterase expression as well as acetylcholinesterase promoter activity during thapsigargin induced apoptosis in HeLa and MDA-MB-435s cells, effects that were also inhibited by BAPTA-AM. We further demonstrated that the transactivation of the human acetylcholinesterase promoter by A23187 and thapsigargin was partially mediated by a CCAAT motif within the -1270 to -1248 fragment of the human acetylcholinesterase promoter. This motif was able to bind to CCAAT binding factor (CBF/NF-Y). These results strongly suggest that cytosolic Ca2+ plays a key role in acetylcholinesterase regulation during apoptosis induced by A23187 and thapsigargin.

Original languageEnglish (US)
Pages (from-to)93-108
Number of pages16
JournalInternational Journal of Biochemistry and Cell Biology
Volume39
Issue number1
DOIs
StatePublished - 2007

Keywords

  • Acetylcholinesterase
  • Apoptosis
  • Ca
  • Transcriptional activity
  • mRNA stability

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Regulation of acetylcholinesterase expression by calcium signaling during calcium ionophore A23187- and thapsigargin-induced apoptosis'. Together they form a unique fingerprint.

Cite this