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Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity.
Open accessAbstract
Tumor necrosis factor (TNF) is selectively cytotoxic to some types of tumor cells in vitro and exerts antitumor activity in vivo. Reactive oxygen intermediates (ROIs) have been implicated in the direct cytotoxic activity of TNF. By using confocal microscopy, flow cytometry, and the ROI-specific probe dihydrorhodamine 123, we directly demonstrate that intracellular ROIs are formed after TNF stimulation. These ROIs are observed exclusively under conditions where cells are sensitive to the cytotoxic activity of TNF, suggesting a direct link between both phenomena. ROI scavengers, such as butylated hydroxyanisole, effectively blocked the formation of free radicals and arrested the cytotoxic response, confirming that the observed ROIs are cytocidal. The mitochondrial glutathione system scavenges the major part of the produced ROIs, an activity that could be blocked by diethyl maleate; under these conditions, TNF-induced ROIs detectable by dihydrorhodamine 123 oxidation were 5- to 20-fold higher.
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Cited by
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Lipton, P. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.4.1431 · Cited by 3,043
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Zhang, D.-W., Shao, J., Lin, J., Zhang, N., Lu, B.-J., Lin, S.-C., Dong, M.-Q., & Han, J. (2009) · Science · doi:10.1126/science.1172308 · Cited by 1,931
Kamata, H., Honda, S.-I., Maeda, S., Chang, L., Hirata, H., & Karin, M. (2005) · Cell · doi:10.1016/j.cell.2004.12.041 · Cited by 1,792
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Metadata
- Authors
- Goossens, V, Grooten, J., De Vos, K., & Fiers, W.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1995-08-29
- Volume
- 92
- Issue
- 18
- Pages
- 8115-8119
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1964390988
- Cited by
- 596
- References
- 0
- FWCI
- 8.88
- Type
- journal article
- Language
- en
- Open access
- green
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- Goossens, V, Grooten, J., De Vos, K., & Fiers, W. (1995). Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.92.18.8115
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