Induction of apoptosis by nitric oxide in macrophages is independent of apoptotic volume decrease.
Apoptosis occurs through a sequence of specific biochemical and morphological alterations that define the progress of cell death. The changes of the mitochondrial inner membrane potential (DeltaPsi(m)), the release of cytochrome c to the cytosol, the apoptotic volume decrease (AVD) and the activation of caspases have been measured in RAW 264.7, HeLa and Jurkat T cells incubated with molecules that induce apoptosis through the mitochondrial pathway. Our data show that NO, staurosporine, etoposide and camptothecin increased DeltaPsi(m) in macrophages but not in HeLa and Jurkat cells, that exhibited a DeltaPsi(m) decrease. Moreover, the apoptosis induced by NO in macrophages, but not that promoted by staurosporine, might occur in the absence of AVD. Analysis of the sequence of apoptotic manifestations shows that DeltaPsi(m) precedes AVD and caspase activation in RAW 264.7 cells. Inhibition of AVD abrogates apoptosis in HeLa and Jurkat T cells regardless of the stimuli used. These data suggest that the changes of DeltaPsi(m) are cell-type dependent and that AVD is dispensable for apoptosis in macrophages.
Hortelano
S
S
Instituto de Bioquímica (Centro Mixto CSIC-UCM), Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
Zeini
M
M
Castrillo
A
A
Alvarez
A M
AM
Boscá
L
L
D017209:Apoptosis; D002166:Camptothecin / Q000494:pharmacology; D048429:Cell Size; D005047:Etoposide / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D008564:Membrane Potentials; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology
D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D005047:Etoposide; D019311:Staurosporine; D002166:Camptothecin