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Title: Involvement of protein kinase C-{beta} and ceramide in tumor necrosis factor-a-induced but not Fas-induced apoptosis of human myeloid leukemia cells.

Abstract

The role of protein kinase C-{beta} (PKC-{beta}) in apoptosis induced by tumor necrosis factor (TNF)-{alpha} and anti-Fas monoclonal antibody (mAb) in the human myeloid HL-60 leukemia cell line was studied by using its variant HL-525, which is deficient in PKC-{beta}. In contrast to the parental HL-60 cells, HL-525 is resistant to TNF-{alpha}-induced apoptosis but sensitive to anti-Fas mAb-induced apoptosis. Both cell types expressed similar levels of the TNF-receptor I, whereas the Fas receptor was detected only in HL-525 cells. Transfecting the HL-525 cells with an expression vector containing PKC-{beta} reestablished their susceptibility to TNF-{alpha}-induced apoptosis. The apoptotic effect of TNF-{alpha} in HL-60 and the transfectants was abrogated by fumonisin, an inhibitor of ceramide generation, and by the peptide Ac-YVAD-BoMK, an inhibitor of caspase-1 and -4. Supplementing HL-525 cells with exogenous ceramides bypassed the PKC-{beta} deficiency and induced apoptosis, which was also restrained by the caspase-1 and -4 inhibitor. The apoptotic effect of anti-Fas mAb in HL-525 cells was abrogated by the antioxidants N-acetylcysteine and glutathione and by the peptide z-DEVD-FMK, an inhibitor of caspase-3 and -7. We suggest that TNF-{alpha}-induced apoptosis involves PKC-{beta} and then ceramide and, in turn, caspase-1 and/or -4, whereas anti-Fas mAb-induced apoptosis utilizes reactive oxygen intermediatesmore » and, in turn, caspase-3 and/or -7.« less

Authors:
; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
OSTI Identifier:
942387
Report Number(s):
ANL/CMB/JA-30864
Journal ID: ISSN 0021-9258; JBCHA3; TRN: US200915%%524
DOE Contract Number:  
DE-AC02-06CH11357
Resource Type:
Journal Article
Journal Name:
J. Biol. Chem.
Additional Journal Information:
Journal Volume: 274; Journal Issue: 33 ; Aug. 13, 1999; Journal ID: ISSN 0021-9258
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; ANTIOXIDANTS; APOPTOSIS; GLUTATHIONE; HUMAN POPULATIONS; LEUKEMIA; LEVELS; MYELOID LEUKEMIA; NECROSIS; NEOPLASMS; OXYGEN; PEPTIDES; PHOSPHOTRANSFERASES; PROTEINS; RECEPTORS; VECTORS

Citation Formats

Laouar, A., Glesne, D., Huberman, E., and Center for Mechanistic Biology and Biotechnology. Involvement of protein kinase C-{beta} and ceramide in tumor necrosis factor-a-induced but not Fas-induced apoptosis of human myeloid leukemia cells.. United States: N. p., 1999. Web. doi:10.1074/jbc.274.33.23526.
Laouar, A., Glesne, D., Huberman, E., & Center for Mechanistic Biology and Biotechnology. Involvement of protein kinase C-{beta} and ceramide in tumor necrosis factor-a-induced but not Fas-induced apoptosis of human myeloid leukemia cells.. United States. doi:10.1074/jbc.274.33.23526.
Laouar, A., Glesne, D., Huberman, E., and Center for Mechanistic Biology and Biotechnology. Fri . "Involvement of protein kinase C-{beta} and ceramide in tumor necrosis factor-a-induced but not Fas-induced apoptosis of human myeloid leukemia cells.". United States. doi:10.1074/jbc.274.33.23526.
@article{osti_942387,
title = {Involvement of protein kinase C-{beta} and ceramide in tumor necrosis factor-a-induced but not Fas-induced apoptosis of human myeloid leukemia cells.},
author = {Laouar, A. and Glesne, D. and Huberman, E. and Center for Mechanistic Biology and Biotechnology},
abstractNote = {The role of protein kinase C-{beta} (PKC-{beta}) in apoptosis induced by tumor necrosis factor (TNF)-{alpha} and anti-Fas monoclonal antibody (mAb) in the human myeloid HL-60 leukemia cell line was studied by using its variant HL-525, which is deficient in PKC-{beta}. In contrast to the parental HL-60 cells, HL-525 is resistant to TNF-{alpha}-induced apoptosis but sensitive to anti-Fas mAb-induced apoptosis. Both cell types expressed similar levels of the TNF-receptor I, whereas the Fas receptor was detected only in HL-525 cells. Transfecting the HL-525 cells with an expression vector containing PKC-{beta} reestablished their susceptibility to TNF-{alpha}-induced apoptosis. The apoptotic effect of TNF-{alpha} in HL-60 and the transfectants was abrogated by fumonisin, an inhibitor of ceramide generation, and by the peptide Ac-YVAD-BoMK, an inhibitor of caspase-1 and -4. Supplementing HL-525 cells with exogenous ceramides bypassed the PKC-{beta} deficiency and induced apoptosis, which was also restrained by the caspase-1 and -4 inhibitor. The apoptotic effect of anti-Fas mAb in HL-525 cells was abrogated by the antioxidants N-acetylcysteine and glutathione and by the peptide z-DEVD-FMK, an inhibitor of caspase-3 and -7. We suggest that TNF-{alpha}-induced apoptosis involves PKC-{beta} and then ceramide and, in turn, caspase-1 and/or -4, whereas anti-Fas mAb-induced apoptosis utilizes reactive oxygen intermediates and, in turn, caspase-3 and/or -7.},
doi = {10.1074/jbc.274.33.23526},
journal = {J. Biol. Chem.},
issn = {0021-9258},
number = 33 ; Aug. 13, 1999,
volume = 274,
place = {United States},
year = {1999},
month = {8}
}