Our previous work has shown that non-toxic concentrations of peroxynitrite nevertheless commit U937 cells to mitochondrial permeability-transition (MPT)-dependent necrosis that is however prevented by a parallel survival signaling pathway involving cytosolic phospholipase A(2) (cPLA2)-dependent arachidonic acid release and PKC alpha activation associated with the cytosolic translocation of Bad. The present study provides evidence of an early mitochondrial translocation of PKC alpha. Inhibition of the survival signaling at the level of either cPLA(2), or PKC, was invariably associated with prevention of the mitochondrial localization of PKC alpha, with the mitochondrial translocation of Bad and Bax and with a very rapid lethal response. Collectively, the results presented in this study demonstrate that peroxynitrite, while committing U937 cells to necrosis, triggers a parallel signaling response leading to the cytosolic localization of two important members of the Bcl-2 family implicated in the onset of MPT.
Peroxynitrite-induced mitochondrial translocation of PKCalpha causes U937 cell survival.
CERIONI, LIANA;PALOMBA, LETIZIA;CANTONI, ORAZIO
2006
Abstract
Our previous work has shown that non-toxic concentrations of peroxynitrite nevertheless commit U937 cells to mitochondrial permeability-transition (MPT)-dependent necrosis that is however prevented by a parallel survival signaling pathway involving cytosolic phospholipase A(2) (cPLA2)-dependent arachidonic acid release and PKC alpha activation associated with the cytosolic translocation of Bad. The present study provides evidence of an early mitochondrial translocation of PKC alpha. Inhibition of the survival signaling at the level of either cPLA(2), or PKC, was invariably associated with prevention of the mitochondrial localization of PKC alpha, with the mitochondrial translocation of Bad and Bax and with a very rapid lethal response. Collectively, the results presented in this study demonstrate that peroxynitrite, while committing U937 cells to necrosis, triggers a parallel signaling response leading to the cytosolic localization of two important members of the Bcl-2 family implicated in the onset of MPT.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
