PROTECTIVE EFFECT OF N-ACETYLCYSTEINE IN TUMOR NECROSIS FACTOR-ALPHA-INDUCED APOPTOSIS IN U937 CELLS - THE ROLE OF MITOCHONDRIA

The existence of two different pathways for cell death has been postul ated. In addition to the passive and traumatic process leading to necr osis, an active program characterized by organelle integrity and calle d apoptosis has been described. A positive correlation between the apo ptotic cell death process and oxidative imbalance has been demonstrate d. In fact, the antioxidant N-acetylcysteine (NAG) seems to be capable of impairing the apoptotic program, replenishing intracellular reduce d glutathione content in cells exposed to tumor necrosis factor-alpha (TNF) as apoptotic inducer. Moreover, protein synthesis inhibitors suc h as cycloheximide (CHX) can facilitate apoptotic triggering by TNF, a nd mitochondrial function was suggested to be essential in the TNF-med iated apoptotic process. With this in mind, a specific analysis using the JC-1 probe, a fluorescent dye which is capable of indicating mitoc hondrial membrane potential (Delta Psi m) changes, was carried out. Ou r results show that TNF exposure is capable of altering the mitochondr ia and that NAC protection from CHX f TNF-induced apoptosis could be d ue to a direct effect of the drug on mitochondrial integrity and funct ion. (C) 1995 Academic Press, Inc.