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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