Defining characteristics of Types I and II apoptotic cells in response to TRAIL.

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.
Authors	Nesrin Ozören, Wafik S El-Deiry
Journal	Neoplasia (New York, N.Y.) (Neoplasia) 2002 Nov-Dec Vol. 4 Issue 6 Pg. 551-7 ISSN: 1522-8002 [Print] United States
PMID	12407450 (Publication Type: Journal Article)
Chemical References	Apoptosis Regulatory Proteins Arabidopsis Proteins BH3 Interacting Domain Death Agonist Protein BID protein, human CASP8 and FADD-Like Apoptosis Regulating Protein CFLAR protein, human Carrier Proteins Cytochrome c Group Enzyme Precursors HSP70 Heat-Shock Proteins Intracellular Signaling Peptides and Proteins Membrane Glycoproteins Proto-Oncogene Proteins c-bcl-2 TNF-Related Apoptosis-Inducing Ligand TNFSF10 protein, human Tumor Necrosis Factor-alpha Fatty Acid Desaturases Fad7 protein, Arabidopsis Poly(ADP-ribose) Polymerases CASP3 protein, human CASP8 protein, human CASP9 protein, human Caspase 3 Caspase 8 Caspase 9 Caspases
Topics	Adenocarcinoma (enzymology, metabolism, pathology) Apoptosis (drug effects) Apoptosis Regulatory Proteins Arabidopsis Proteins BH3 Interacting Domain Death Agonist Protein Blotting, Western CASP8 and FADD-Like Apoptosis Regulating Protein Carcinoma, Non-Small-Cell Lung (enzymology, metabolism, pathology) Carrier Proteins (metabolism) Caspase 3 Caspase 8 Caspase 9 Caspases (metabolism) Child Colonic Neoplasms (drug therapy, enzymology, pathology) Cytochrome c Group (metabolism) Enzyme Precursors (metabolism) Fatty Acid Desaturases (metabolism) HSP70 Heat-Shock Proteins (metabolism) Hepatocytes (cytology, enzymology) Humans Intracellular Signaling Peptides and Proteins Lung Neoplasms (enzymology, metabolism, pathology) Male Membrane Glycoproteins (pharmacology) Mitochondria (physiology) Poly(ADP-ribose) Polymerases (metabolism) Precipitin Tests Proto-Oncogene Proteins c-bcl-2 (metabolism) Subcellular Fractions TNF-Related Apoptosis-Inducing Ligand Tumor Cells, Cultured Tumor Necrosis Factor-alpha (pharmacology)

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