The early phase of apoptosis in human neuroblastoma CHP100 cells is characterized by lipoxygenase-dependent ultraweak light emission

Human neuroblastoma CHP100 cells were forced into apoptosis (programmed cel l death, PCD) or necrosis by treatment with calcium chloride or sodium nitr oprusside (a nitric oxide donor), respectively. Cellular luminescence, a ma rker of membrane lipid peroxidation, was increased by calcium but not by ni troprusside, and reached a maximum of 4-fold the control value 2 hours afte r treatment. The increase in luminescence was paralleled by increased 5-lip oxygenase (up to 250% of the control value) and decreased catalase (down to 50%) activity within the same time window, Consistently, incubation of CHP 100 cells with inhibitors of 5-lipoxygenase (5,8,11,14-eicosatetraynoic aci d and MK886) reduced light emission and PCD, whereas inhibition of catalase by 3-amino-1,2,4-triazole enhanced both processes. Treatment of CHP100 cel ls with retinoic acid or cisplatin, unrelated PCD inducers reported to acti vate the lipoxygenase pathway, also gave enhanced light emission parallel t o PCD increase. Altogether, these results suggest that cellular luminescenc e is an early marker of apoptotic, but not necrotic, program(s) involving g eneration of hydrogen peroxide and activation of 5-lipoxygenase. (C) 1999 A cademic Press.