Phosphatidylserine externalization during differentiation-triggered apoptosis of erythroleukemic cells

Cecilia Diaz, Anh Tuyet Lee, David J. McConkey, Alan J. Schroit

Research output: Contribution to journalArticle

22 Citations (Scopus)

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-x(L), and decrease in mitochondrial transmembrane potential (ΔΨ(m)) that ultimately resulted in cell death. Reorientation of phosphatidyl-serine (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 ΔΨ(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 ΔΨ(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 ΔΨ(m), but independent of BCL-2 and caspases.

Original languageEnglish (US)
Pages (from-to)218-226
Number of pages9
JournalCell Death and Differentiation
Volume6
Issue number3
StatePublished - Mar 1999

Fingerprint

Hemin
Phosphatidylserines
DNA Fragmentation
Dactinomycin
Apoptosis
Caspase 2
Phospholipid Transfer Proteins
Leukemia, Erythroblastic, Acute
Caspase Inhibitors
K562 Cells
Membrane Potentials
Cell Death
Down-Regulation
Cell Membrane
Lipids
Proteins

Keywords

  • Apoptosis
  • BCL-2
  • BCL-x(L)
  • Differentiation
  • Phosphatidlyserine

ASJC Scopus subject areas

  • Cell Biology

Cite this

Phosphatidylserine externalization during differentiation-triggered apoptosis of erythroleukemic cells. / Diaz, Cecilia; Lee, Anh Tuyet; McConkey, David J.; Schroit, Alan J.

In: Cell Death and Differentiation, Vol. 6, No. 3, 03.1999, p. 218-226.

Research output: Contribution to journalArticle

Diaz, Cecilia ; Lee, Anh Tuyet ; McConkey, David J. ; Schroit, Alan J. / Phosphatidylserine externalization during differentiation-triggered apoptosis of erythroleukemic cells. In: Cell Death and Differentiation. 1999 ; Vol. 6, No. 3. pp. 218-226.
@article{9d7e548d8b9d443ebacc72343c0831d3,
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-x(L), and decrease in mitochondrial transmembrane potential (ΔΨ(m)) that ultimately resulted in cell death. Reorientation of phosphatidyl-serine (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 ΔΨ(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 ΔΨ(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 ΔΨ(m), but independent of BCL-2 and caspases.",
keywords = "Apoptosis, BCL-2, BCL-x(L), Differentiation, Phosphatidlyserine",
author = "Cecilia Diaz and Lee, {Anh Tuyet} and McConkey, {David J.} and Schroit, {Alan J.}",
year = "1999",
month = "3",
language = "English (US)",
volume = "6",
pages = "218--226",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Phosphatidylserine externalization during differentiation-triggered apoptosis of erythroleukemic cells

AU - Diaz, Cecilia

AU - Lee, Anh Tuyet

AU - McConkey, David J.

AU - Schroit, Alan J.

PY - 1999/3

Y1 - 1999/3

N2 - 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-x(L), and decrease in mitochondrial transmembrane potential (ΔΨ(m)) that ultimately resulted in cell death. Reorientation of phosphatidyl-serine (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 ΔΨ(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 ΔΨ(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 ΔΨ(m), but independent of BCL-2 and caspases.

AB - 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-x(L), and decrease in mitochondrial transmembrane potential (ΔΨ(m)) that ultimately resulted in cell death. Reorientation of phosphatidyl-serine (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 ΔΨ(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 ΔΨ(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 ΔΨ(m), but independent of BCL-2 and caspases.

KW - Apoptosis

KW - BCL-2

KW - BCL-x(L)

KW - Differentiation

KW - Phosphatidlyserine

UR - http://www.scopus.com/inward/record.url?scp=0032970132&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032970132&partnerID=8YFLogxK

M3 - Article

C2 - 10200572

AN - SCOPUS:0032970132

VL - 6

SP - 218

EP - 226

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 3

ER -