Differential role of extra- and intracellular superoxide anions for nitric oxide-mediated apoptosis induction
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Published on: December 21, 2011
Mareike Steinmann1, Nicolas Moosmann, Mareike Schimmel
1Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene Universität Freiburg, D-79104 Freiburg, Germany.
Abstract:
Nitric oxide (NO) has recently been shown to mediate apoptosis induction selectively in transformed fibroblasts, in contrast to their nontransformed parental cells. Here we show that NO-mediated apoptosis induction in transformed fibroblasts can be divided into two major phases. During phase 1, peroxynitrite is generated by the interaction of extracellular superoxide anions with NO and the intracellular glutathione level is subsequently lowered. This defines the beginning of phase 2, in which NO-mediated signaling depends on intracellular superoxide anions exclusively. The resultant peroxynitrite seems to activate the mitochondrial permeability transition pore and thus triggers execution of apoptosis. Experimental depletion of intracellular glutathione causes a drastic decrease in the length of phase 1 in transformed cells and renders nontransformed cells sensitive to NO-mediated apoptosis induction. These findings allow the prediction that either induction of superoxide anion generation or glutathione depletion may render cells sensitive to NO-mediated apoptosis induction.
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Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...

