Bax-dependent apoptosis induced by ceramide in HL-60 cells.
Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. In this study, we show that antisense bax inhibits cytochrome c release, poly(ADP-ribose)polymerase cleavage and cell death induced by ceramide in HL-60 cells. In addition, ceramide induces translocation of Bax to mitochondria. The addition of the broad spectrum caspase inhibitor zVAD-fmk prevented ceramide-induced apoptotic cell death but did not inhibit translocation of Bax and mitochondrial cytochrome c release. Furthermore, ceramide inhibits the expression of the antiapoptotic protein Bcl-xL with an increase in the ratio of Bax to Bcl-xL. These data provide direct evidence that Bax plays an important role in regulating ceramide-induced apoptosis.
Kim
H J
HJ
Division of Biochemistry, College of Pharmacy, Chung-Ang Uuniversity, Seoul 156-756, South Korea.
Mun
J Y
JY
Chun
Y J
YJ
Choi
K H
KH
Kim
M Y
MY
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D002518:Ceramides / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism; D053938:DNA Fragmentation; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009841:Oligonucleotides / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000590:Amino Acid Chloromethyl Ketones; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D002518:Ceramides; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C101954:N-caproylsphingosine; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases