Abstract
Type I cells have been defined to be independent of mitochondria for the induction of Fas death receptor-mediated apoptosis, whereas Type II cells are mitochondria-dependent. Knock-out studies in mice show that thymocytes are Type I and liver cells are Type II. We have previously shown that primary human hepatocytes and HCT116 human colon carcinoma cells behave like Type II cells because TRAIL-induced apoptosis can be blocked by the caspase 9 inhibitor, Z-LEHD-FMK. On the other hand, caspase 9 inhibition does not allow survival of TRAIL-treated SW480 colon cancer cells, which is predicted for Type I cells. Investigating the differences in TRAIL-induced apoptotic pathways in HCT116 and SW480 cells revealed that although FADD, BID, and procaspase 3 protein levels are higher in SW480 cells, and although procaspase 8 and FLIP processing is more efficient at the TRAIL-DISC of SW480 cells, BID, procaspase 3, XIAP, and PARP cleavages occur more rapidly in HCT116, despite the higher levels of BCL-2 and HSP70. Cytochrome c release from the mitochondria to the cytoplasm is more efficient in HCT116 cells. These results suggest BID cleavage as a possible limiting factor in the involvement of mitochondria in TRAIL-induced cell death. Thus, regulation of BID cleavage may define if a cell is mitochondria-dependent or -independent in response to TRAIL death receptor-induced apoptosis.
MeSH terms
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Adenocarcinoma / enzymology
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Adenocarcinoma / metabolism*
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Adenocarcinoma / pathology
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Apoptosis / drug effects*
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Apoptosis Regulatory Proteins
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Arabidopsis Proteins*
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BH3 Interacting Domain Death Agonist Protein
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Blotting, Western
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CASP8 and FADD-Like Apoptosis Regulating Protein
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Carcinoma, Non-Small-Cell Lung / enzymology
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Carcinoma, Non-Small-Cell Lung / metabolism*
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Carcinoma, Non-Small-Cell Lung / pathology
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Carrier Proteins / metabolism*
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Caspase 3
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Caspase 8
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Caspase 9
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Caspases / metabolism
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Child
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Colonic Neoplasms / drug therapy
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Colonic Neoplasms / enzymology
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Colonic Neoplasms / pathology
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Cytochrome c Group / metabolism
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Enzyme Precursors / metabolism
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Fatty Acid Desaturases / metabolism
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HSP70 Heat-Shock Proteins / metabolism
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Hepatocytes / cytology
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Hepatocytes / enzymology*
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Humans
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Intracellular Signaling Peptides and Proteins*
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Lung Neoplasms / enzymology
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Lung Neoplasms / metabolism*
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Lung Neoplasms / pathology
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Male
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Membrane Glycoproteins / pharmacology*
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Mitochondria / physiology*
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Poly(ADP-ribose) Polymerases / metabolism
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Precipitin Tests
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Subcellular Fractions
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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Apoptosis Regulatory Proteins
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Arabidopsis Proteins
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BH3 Interacting Domain Death Agonist Protein
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BID protein, human
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CASP8 and FADD-Like Apoptosis Regulating Protein
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CFLAR protein, human
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Carrier Proteins
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Cytochrome c Group
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Enzyme Precursors
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HSP70 Heat-Shock Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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Proto-Oncogene Proteins c-bcl-2
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Tumor Necrosis Factor-alpha
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Fatty Acid Desaturases
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Fad7 protein, Arabidopsis
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Poly(ADP-ribose) Polymerases
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CASP3 protein, human
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CASP8 protein, human
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CASP9 protein, human
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Caspase 3
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Caspase 8
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Caspase 9
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Caspases