Inhibition of trifluoperazine-induced DNA fragmentation by cyclic AMP mediated signaling

Ung Gu Kang, Myung Jong Kim, Pann Ghill Suh, Sung Ho Ryu, Joo Bae Park, Jung Hye Kim, Yong Sik Kim, Young Han Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Trifluoperazine (TFP), a phenothiazine antipsychotic agent with calmodulin antagonist property, induces DNA fragmentation in a dose- and time-dependent manner in PC12 cells. Various agents affecting calcium mediated intracellular signal transduction such as calcium chelators, calcium ionopores, inhibitors of phospholipase C, and activators/inhibitors of protein kinase C did not block TFP-induced DNA fragmentation. Some of these agents themselves induced DNA fragmentation in the conditions under which they were examined. However, cholera toxin (selective Gs activator), forskolin (adenylate cyclase activator) or dibutyryl cyclic AMP (cyclic AMP analogue) inhibited TFP-induced DNA fragmentation in a dose-dependent manner. These results suggest that it is not the calcium but the Gs and adenylate cyclase pathways that play an important role in TFP-induced DNA fragmentation in PC12 cells.

Original languageEnglish (US)
Pages (from-to)596-602
Number of pages7
JournalMolecules and Cells
Volume9
Issue number6
StatePublished - Dec 31 1999

Keywords

  • Calcium
  • Calmodulin
  • Cyclic AMP
  • DNA Fragmentation
  • PC12 Cell
  • Trifluoperazine

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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