Ja. Sanchezalcazar et al., TUMOR-NECROSIS-FACTOR-ALPHA INCREASES ATP CONTENT IN METABOLICALLY INHIBITED L929 CELLS PRECEDING CELL-DEATH, The Journal of biological chemistry, 272(48), 1997, pp. 30167-30177
The effects of tumor necrosis factor-alpha (TNF) on ATP levels were st
udied in metabolically inhibited L929 cells. Treatment of these cells
with TNF in the presence of actinomycin D or cycloheximide induces cyc
lic changes in the intracellular ATP content preceding cell death. Aft
er 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 h
ours later, it increased again by 23 +/- 5% over the control level (p
< 0.001). Coinciding with cell death, ATP content decreased progressiv
ely 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 electr
on transport prevented the increase in cellular ATP, the formation of
reactive oxygen species, and the apoptotic cell death caused by TNF. W
e suggest that the TNF/actinomycin Dor TNF/cycloheximide-induced chang
es in intracellular ATP levels may be involved in the cytotoxic effect
of TNF in metabolically inhibited L929 cells.