title: Phosphatidylserine externalization during differentiation-triggered apoptosis of erythroleukemic cells.
abstract: K562 erythroleukemia cells undergo apoptosis when induced to differentiate along the erythroid lineage with hemin. This event, characterized by DNA fragmentation, correlated with downregulation of the survival protein, BCL-xL, and decrease in mitochondrial transmembrane potential (deltapsi[m]) that ultimately resulted in cell death. Reorientation of phosphatidylserine (PS) from the cells inner-to-outer plasma membrane leaflet and inhibition of the aminophospholipid translocase was observed upon hemin-treatment. Constitutive expression of BCL-2 did not inhibit hemin-induced alterations in lipid asymmetry or decrease in deltapsi[m], and only moderately prevented DNA fragmentation. BCL-2, on the other hand, effectively inhibited actinomycin D-induced DNA fragmentation, the appearance of PS at the cells outer leaflet and the decrease in deltapsi[m]. The caspase inhibitor, z.VAD.fmk, blocked DNA fragmentation by both hemin and actinomycin D, but inhibited PS externalization only in the actinomycin D-treated cells. These results suggest that, unlike pharmacologically-induced apoptosis, PS externalization triggered by differentiation-induced apoptosis occurs by a mechanism that is associated with a decrease in deltapsi[m], but independent of BCL-2 and caspases.
authors: The Department of Cell Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors: C
authors: C
authors: Diaz
authors: A T
authors: AT
authors: Lee
authors: D J
authors: DJ
authors: McConkey
authors: A J
authors: AJ
authors: Schroit
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D061945:Caspase Inhibitors; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation; D003609:Dactinomycin / Q000494:pharmacology; D004920:Erythropoiesis; D015870:Gene Expression; D019254:Genes, bcl-2; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology*; D010718:Phosphatidylserines / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051020:bcl-X Protein
chemical_list: D000590:Amino Acid Chloromethyl Ketones; C494811:BCL2L1 protein, human; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D010718:Phosphatidylserines; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D003609:Dactinomycin; D006427:Hemin