Blood cells with reduced mitochondrial membrane potential and cytosolic cytochrome C can survive and maintain clonogenicity given appropriate signals to suppress apoptosis

Quan Chen, Naoshi Takeyama, Ged Brady, Alastair J M Watson, Caroline Dive

Research output: Contribution to journalArticlepeer-review

Abstract

Reduction of mitochondrial membrane potential (Ψ(m)) and release of cytochrome c from mitochondria appear to be key events during apoptosis. Apoptosis was induced in IC.DP premast cells by the withdrawal of interleukin-3 (IL-3). Ψ(m) decreased by 12 hours and cytochrome c was detected in the cytosol at 18 hours. Despite these changes in the mitochondria after 18 hours of IL-3 deprivation, clonogenicity was unaffected when IL-3 was replenished at 18 hours. Activation of v-Abl tyrosine kinase (v-Abl TK) in IC.DP cells before IL-3 depletion led to increased levels of Bcl-X(L), prevented reduction of Ψ(m) and the release of mitochondrial cytochrome c, and suppressed apoptosis. Activation of v-Abl TK 18 hours after withdrawal of IL-3 when ≤10% of the cells had died restored Ψ(m) in the remaining cells. More than 40% of cells thus rescued by v-Abl TK between 18 and 42 hours could subsequently form colonies in the presence of IL-3. These data suggest that reduction in Ψ(m) precedes loss of mitochondrial cytochrome c in IC.DP cells; that v-Abl TK activation, probably via upregulation of Bcl-X(L), prevents loss of Ψ(m) and blocks the release of cytochrome c from mitochondria; and that neither of these mitochondrial events is sufficient for commitment to apoptosis.
Original languageEnglish
Pages (from-to)4545-4553
Number of pages8
JournalBlood
Volume92
Issue number12
Publication statusPublished - 15 Dec 1998

Keywords

  • Animals
  • *Apoptosis
  • Blood Cells/*metabolism
  • Cell Line
  • Cell Survival/drug effects/physiology
  • Colony-Forming Units Assay
  • Cytochrome c Group/*metabolism
  • Cytosol/metabolism
  • Enzyme Activation/drug effects
  • Interleukin-3/pharmacology/physiology
  • Mast Cells/cytology/metabolism
  • Membrane Potentials/physiology
  • Mice
  • Mitochondria/metabolism/*physiology
  • Oncogene Proteins v-abl/metabolism
  • Temperature
  • Time Factors

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