Phosphatidylcholine-specific phospholipase C inhibitor, tricyclodecan-9- yl xanthogenate (D609), increases phospholipase D-mediated phosphatidylcholine hydrolysis in UMR-106 osteoblastic osteosarcoma cells

Amareshwar Singh*, Julie M. Radeff, Joseph G. Kunnel, Paula H Stern

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Our previous studies have shown that parathyroid hormone (PTH) stimulates phosphatidylcholine (PC) hydrolysis by phospholipase D (PLD) and transphosphatidylation in UMR-106 osteoblastic cells. To determine whether phospholipase C (PLC) is also involved in the PTH-mediated PC hydrolysis, we used the inhibitor, tricyclodecan-9-yl xanthogenate (D609), a putatively selective antagonist of this pathway. Consistent with this proposed mechanism, D609 decreased 3H-phosphocholine in extracts from UMR-106 cells prelabeled with 3H-choline. Unexpectedly, D609 enhanced PC hydrolysis and transphosphatidylation, suggesting that either there was a compensatory increase in PLD activity when PLC was inhibited, or that D609 directly increased PLD activity. The D609-stimulated increase in PC hydrolysis was rapid, being seen as early as 2 min. The effect of D609 was temperature- sensitive, consistent with an enzymatic mechanism. The D609-stimulated increase in PC hydrolysis was PKC-independent, based upon the lack of effect of down-regulation of PKC by phorbol 12,13-dibutyrate on the response. The studies reveal a novel action of this inhibitor on signaling in osteoblastic cells which might influence downstream responses. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)201-208
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1487
Issue number2-3
DOIs
StatePublished - Sep 27 2000

Keywords

  • Osteoblast
  • Parathyroid hormone
  • Phosphatidylcholine
  • Phospholipase C
  • Phospholipase D
  • Protein kinase C
  • Tricyclodecan-9-yl xanthogenate

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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