title: 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.affiliation: Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Philadelphia, PA 19104, USA.
authors.forename: Nesrin
authors.initials: N
authors.lastname: Ozören
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D029681:Arabidopsis Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; D015153:Blotting, Western; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002648:Child; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D003574:Cytochrome c Group / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008928:Mitochondria / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011233:Precipitin Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013347:Subcellular Fractions; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D029681:Arabidopsis Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D003574:Cytochrome c Group; D004792:Enzyme Precursors; D018840:HSP70 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases