Related Experiment Videos
Tumor necrosis factor-mediated cytotoxicity involves ADP-ribosylation
S Agarwal1, B E Drysdale, H S Shin
1Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Journal of Immunology (Baltimore, Md. : 1950)
|June 15, 1988
Summary
Tumor necrosis factor (TNF) triggers cell death by increasing ADP-ribosylation in target cells. Inhibiting this process with specific compounds prevented TNF-induced cytotoxicity, suggesting ADP-ribosylation
Area of Science:
- Cellular Biology
- Immunology
- Biochemistry
Background:
- Tumor necrosis factor (TNF) is a key cytokine involved in inflammation and cell death.
- The precise molecular mechanisms underlying TNF-mediated cytotoxicity are not fully elucidated.
- ADP-ribosylation is a post-translational modification with diverse cellular roles.
Purpose of the Study:
- To investigate the role of ADP-ribosylation in TNF-induced cytotoxicity.
- To determine if inhibiting ADP-ribosylation affects TNF's cytotoxic effects on cancer cells.
Main Methods:
- Studied TNF-mediated cytotoxicity in L929 murine fibroblasts and ME-180 human cervical carcinoma cells.
- Measured ADP-ribosylation levels, intracellular NAD+ and ATP concentrations.
- Utilized ADP-ribosylation inhibitors (3-aminobenzamide, nicotinamide) to assess their impact on TNF cytotoxicity.
Main Results:
- TNF exposure led to a time- and dose-dependent increase in ADP-ribosylation in L929 and ME-180 cells, correlating with cell death.
- Intracellular NAD+ and ATP levels decreased during TNF-induced cell death.
- Inhibitors of ADP-ribosylation, 3-aminobenzamide and nicotinamide, significantly reduced TNF-mediated cytotoxicity in both cell lines.
Conclusions:
- ADP-ribosylation is implicated in the mechanism of TNF-mediated cytotoxicity.
- Targeting ADP-ribosylation represents a potential strategy to modulate TNF's cytotoxic effects.