Differentiation-induced HL-60 cell apoptosis: a mechanism independent of mitochondrial disruption?

Autor: Belinda T. Doyle, Amanda O'Neill, R. W. G. Watson, John M. Fitzpatrick
Rok vydání: 2004
Předmět:
Cancer Research
Clinical Biochemistry
Blotting
Western
Pharmaceutical Science
Apoptosis
HL-60 Cells
Mitochondrion
Mitochondrial apoptosis-induced channel
Permeability
Mitochondrial Proteins
Antigens
CD
Humans
Inner mitochondrial membrane
Caspase
bcl-2-Associated X Protein
Pharmacology
CD11b Antigen
biology
Chemistry
Cytochrome c
Biochemistry (medical)
Intracellular Signaling Peptides and Proteins
Cytochromes c
Cell Differentiation
Cell Biology
Intracellular Membranes
Molecular biology
Caspase Inhibitors
Recombinant Proteins
Cell biology
Mitochondria
Mitochondrial permeability transition pore
Proto-Oncogene Proteins c-bcl-2
Caspases
biology.protein
Apoptosome
biological phenomena
cell phenomena
and immunity
Apoptosis Regulatory Proteins
Carrier Proteins
BH3 Interacting Domain Death Agonist Protein
Zdroj: Apoptosis : an international journal on programmed cell death. 9(3)
ISSN: 1360-8185
Popis: HL-60 cell differentiation into neutrophil like cells is associated with their induction of apoptosis. We investigated the cellular events that occur pre and post mitochondrial permeability transition to determine the role of the mitochondria in the induction of differentiation induced apoptosis. Pro-apoptotic Bax was translocated to and cleaved at the mitochondrial membrane in addition to t-Bid activation. These processes contributed to mitochondrial membrane disruption and the release of cytochrome c and Smac/DIABLO. The release of cytochrome c was caspase independent, as the caspase inhibitor Z-VAD.fmk, which inhibited apoptosis, did not block the release of cytochrome c. In contrast, the release of Smac/DIABLO was partially inhibited by caspase inhibition indicating differential release pathways for these mitochondrial pro-apoptotic factors. In addition to caspase inhibition we assessed the effects of the Bcl-2 anti-apoptotic family on differentiation induced apoptosis. BH4-Bcl-xl-TAT recombinant protein did not delay apoptosis, but did block the release of cytochrome c and Smac/DIABLO. Bcl-2 over-expression also inhibited differentiation induced apoptosis but was associated with the inhibition of the differentiation process. Differentiation mediated mitochondrial release of cytochrome c and Smac/DIABLO, may not trigger the induction of apoptosis, as BH4-Bclxl-TAT blocks the release of pro-apoptotic factors from the mitochondria, but does not prevent apoptosis.
Databáze: OpenAIRE
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