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 postulated. In addition to the passive and traumatic process leading to necrosis, an active program characterized by organelle integrity and called apoptosis has been described. A positive correlation between the apoptotic cell death process and oxidative imbalance has been demonstrated. In fact, the antioxidant N-acetylcysteine (NAC) seems to be capable of impairing the apoptotic program, replenishing intracellular reduced glutathione content in cells exposed to tumor necrosis factor-alpha (TNF) as apoptotic inducer. Moreover, protein synthesis inhibitors such as cycloheximide (CHX) can facilitate apoptotic triggering by TNF, and mitochondrial function was suggested to be essential in the TNF-mediated apoptotic process. With this in mind, a specific analysis using the JC-1 probe, a fluorescent dye which is capable of indicating mitochondrial membrane potential (delta psi m) changes, was carried out. Our results show that TNF exposure is capable of altering the mitochondria and that NAC protection from CHX + TNF-induced apoptosis could be due to a direct effect of the drug on mitochondrial integrity and function.
Cossarizza
A
A
Department of Biomedical Sciences, University of Modena, Italy.
Franceschi
C
C
Monti
D
D
Salvioli
S
S
Bellesia
E
E
Rivabene
R
R
Biondo
L
L
Rainaldi
G
G
Tinari
A
A
Malorni
W
W
D000111:Acetylcysteine / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles; D002232:Carbocyanines; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006706:Homeostasis; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000975:Antioxidants; D001562:Benzimidazoles; D002232:Carbocyanines; D005456:Fluorescent Dyes; D014409:Tumor Necrosis Factor-alpha; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D003513:Cycloheximide; D000111:Acetylcysteine