Redox regulation of apoptosis in interleukin-3-dependent haemopoietic cells: absence of alteration in both mitochondrial membrane potential (delta psi(m)) and free radical production during apoptosis induced by IL3 withdrawal.
Apoptosis in haemopoietic cells has been linked to the production of free radicals and reduction in mitochondrial transmembrane potential, delta psi(m). We have found that apoptosis in murine IL3-dependent haemopoietic cells induced by IL3 withdrawal lowers a principal source of anti-oxidant (reduced glutathione) but does not increase free radicals nor affect delta psi(m). Increased free radicals are, however, produced during IL3 signalling. Artificially increasing intracellular free radicals by depleting internal glutathione mimics IL3 signalling in that cells maintain shape and are transiently stimulated into S-phase in the absence of IL3. Conversely, depletion of free radicals by anti-oxidants accelerates apoptosis both in the presence and absence of IL3. Our studies suggest that redox conditions rather than free radicals or mitochondrial membrane potential per se may play a significant role in maintaining cell and replicative integrity, and in determining apoptosis in haemopoietic cells.
Garland
J M
JM
Institute of Clinical Science, F.O.R.C.E. Cancer Research Laboratories, Exeter University, Wonford.
Søndergaard
K L
KL
Jolly
J
J
D017209:Apoptosis / Q000187:drug effects; D002450:Cell Communication / Q000502:physiology; D048429:Cell Size; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006019:Glycolysis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology*; D008298:Maleates / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D010084:Oxidation-Reduction; D016196:S Phase / Q000187:drug effects
D005609:Free Radicals; D007377:Interleukin-3; D008298:Maleates; D004247:DNA; C014476:diethyl maleate; D005978:Glutathione