Cross-Talk between Ceramide and PKC Activity in the Control of Apoptosis in WEHI-231

  • Steven J. Chmura
  • Edwardine Nodzenski
  • Mary A. Crane
  • Subbulakshmi Virudachalam
  • Dennis E. Hallahan
  • Ralph R. Weichselbaum
  • Jose Quintans
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 406)


WEHI-231, a murine B-cell lymphoma, readily undergoes programmed cell death following surface immunoglobulin (Ig) cross-linking [1]. Ceramide has been shown to induce apoptosis in WEHI-231 following its exposure to anti-Ig antibodies, dexamethasone, and irradiation [2]. Recently, Haimovitz-Friedman et al. have demonstrated in endothelial cells that PMA not only prevented ceramide mediated apoptosis, but inhibited the generation of ceramide following irradiation [3]. In this paper we use highly specific PKC inhibitors to explore the connection between PKC activity, ceramide signaling and apoptosis. Both chelerythrine chloride and calphostin C triggered rapid apoptosis in WEHI-231 and acted in synergy with exogenous ceramide to induce apoptosis. Detailed studies of chelerythrine’s mechanism of action revealed that 30 minutes following addition of 1011M chelerythrine, sphingomyelin and phosphatidylcholine (PC) mass decreased confirming our previous findings of neutral, but not acidic, sphingomyelinase activation following treatment with PKC inhibitors [4]. The novel observation that inhibition of PKC isoforms present in WEHI-231 leads to a rapid rise in cellular ceramide as a result of sphingomyelin hydrolysis further suggests an antagonistic relationship between PKC activity and ceramide in the signaling events preceding apoptosis.


Phosphatidic Acid Ceramide Production Ceramide Accumulation Ceramide Generation Phosphotransferase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Steven J. Chmura
    • 1
  • Edwardine Nodzenski
    • 2
  • Mary A. Crane
    • 3
  • Subbulakshmi Virudachalam
    • 2
  • Dennis E. Hallahan
    • 2
  • Ralph R. Weichselbaum
    • 2
  • Jose Quintans
    • 1
  1. 1.Department of PathologyUniversity of Chicago and the Pritzker School of MedicineChicagoUSA
  2. 2.Department of Radiation and Cellular OncologyUniversity of Chicago and the Pritzker School of MedicineChicagoUSA
  3. 3.Division of Biological SciencesUniversity of Chicago and the Pritzker School of MedicineChicagoUSA

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