Evidence that protein kinase Cepsilon mediates phorbol ester inhibition of calphostin C- and tumor necrosis factor-alpha-induced apoptosis in U937 histiocytic lymphoma cells.

Abstract

Protein kinase C (PKC) activators, such as the tumor-promoting phorbol esters, have been reported to protect several cell lines from apoptosis induced by a variety of agents. Recent evidence suggests that PKCepsilon is involved in protection of cardiac myocytes from hypoxia-induced cell death (Gray, M. O., Karliner, J. S., and Mochly-Rosen, D. (1997) J. Biol. Chem. 272, 30945-30951). We investigated the protective effects of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on U937 histiocytic lymphoma cells induced to undergo apoptosis by tumor necrosis factor-alpha (TNF-alpha) or by the specific PKC inhibitor calphostin C. U937 cells were transiently permeabilized with a peptide (epsilonV1-2) derived from the V1 region of PKCepsilon that has been reported to specifically block translocation of PKCepsilon. The epsilonV1-2 peptide blocked the inhibitory effect of TPA on both TNF-alpha- and calphostin C-induced apoptosis. A scrambled version of epsilonV1-2 and a peptide reported to inhibit PKCbeta translocation (betaC2-4) had no effect on the ability of TPA to inhibit apoptosis. These results suggest that PKCepsilon is required for the protective effect of TPA in TNF-alpha- and calphostin C-induced apoptosis. Furthermore, calphostin C reduced membrane-associated PKCepsilon activity and immunoreactivity, suggesting that PKCepsilon may play an important role in leukemic cell survival.

• Authors: G C Mayne, A W Murray
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 273 Issue 37 Pg. 24115-21 (Sep 11 1998) ISSN: 0021-9258 [Print] United States
• PMID: 9727032 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromatin
• Enzyme Inhibitors
• Isoenzymes
• Naphthalenes
• Nucleosomes
• Peptide Fragments
• Tumor Necrosis Factor-alpha
• PRKCE protein, human
• Protein Kinase C
• Protein Kinase C-epsilon
• calphostin C
• Tetradecanoylphorbol Acetate

Topics

• Apoptosis (drug effects, physiology)
• Chromatin (drug effects, physiology)
• DNA Fragmentation
• Enzyme Inhibitors (pharmacology)
• Humans
• Isoenzymes (antagonists & inhibitors, chemistry, metabolism)
• Kinetics
• Lymphoma, Large B-Cell, Diffuse
• Naphthalenes (pharmacology)
• Nucleosomes (drug effects, physiology)
• Peptide Fragments (pharmacology)
• Protein Kinase C (antagonists & inhibitors, chemistry, metabolism)
• Protein Kinase C-epsilon
• Tetradecanoylphorbol Acetate (pharmacology)
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (pharmacology, physiology)