Tumor Necrosis Factor-α Increases ATP Content in Metabolically Inhibited L929 Cells Preceding Cell Death

• Published in: The Journal of biological chemistry Vol. 272; no. 48; pp. 30167 - 30177
• Main Authors: Sánchez-Alcázar, José A., Ruı́z-Cabello, Jesús, Hernández-Muñoz, Inmaculada, Pobre, Pilar Sánchez, de la Torre, Paz, Siles-Rivas, Eva, Garcı́a, Inmaculada, Kaplan, Ofer, Muñoz-Yagüe, Marı́a T., Solı́s-Herruzo, José A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28-11-1997
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Triphosphate - metabolism; Animals; Cell Death - drug effects; Cycloheximide - pharmacology; Cytoplasm - metabolism; Dactinomycin - pharmacology; DNA Fragmentation; Dose-Response Relationship, Drug; Electron Transport - drug effects; Humans; L Cells; Lactates - metabolism; Mice; Mitochondria - metabolism; Oligomycins - pharmacology; Oxidative Phosphorylation - drug effects; Protein Synthesis Inhibitors - pharmacology; Reactive Oxygen Species - metabolism; Time Factors; Tumor Necrosis Factor-alpha - pharmacology; Uncoupling Agents - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.48.30167

The effects of tumor necrosis factor-α (TNF) on ATP levels were studied in metabolically inhibited L929 cells. Treatment of these cells with TNF in the presence of actinomycin D or cycloheximide induces cyclic changes in the intracellular ATP content preceding cell death. After 3 h of incubation, the intracellular ATP content increased by 48 ± 6% (p < 0.001), but at 4 h, it decreased to the control level. Two hours later, it increased again by 23 ± 5% over the control level (p < 0.001). Coinciding with cell death, ATP content decreased progressively until almost complete depletion. These changes in ATP content were associated with parallel alterations in the respiratory coupling and with increased generation of reactive oxygen species. The mechanism by which TNF/actinomycin D or TNF/cycloheximide increased cellular ATP seemed to be dependent on the mitochondrial ATP synthesis and related to the cytotoxic effect of TNF, since blockade of mitochondrial electron transport prevented the increase in cellular ATP, the formation of reactive oxygen species, and the apoptotic cell death caused by TNF. We suggest that the TNF/actinomycin D- or TNF/cycloheximide-induced changes in intracellular ATP levels may be involved in the cytotoxic effect of TNF in metabolically inhibited L929 cells.