Effect of ethanol on tumor necrosis factor signaling during liver regeneration.
OBJECTIVES: The liver has tremendous regenerative capacity but can be damaged by toxins, such as ethanol (EtOH). It has long been known that EtOH inhibits liver regeneration. Recent work demonstrates that the proinflammatory cytokine, tumor necrosis factor ( (TNF), is required for normal liver regeneration, as well as for EtOH-related liver damage. Therefore, it is conceivable that EtOH promotes liver damage by altering TNF signal transduction in such a way that proliferative signals are aborted and death signals predominate. DESIGN AND METHODS: Anti-TNF antibodies were used to characterize the TNF signals that are induced in the regenerating liver after two-thirds (partial) hepatectomy (PH) in normal mice and rats. Then, these TNF-regulated processes were evaluated in animals that had been fed nutritionally replete, EtOH-containing diets for several weeks before PH. RESULTS: During normal liver regeneration, TNF induces potentially dangerous responses, such as increased mitochondrial ROS production, but also promotes the activation of several factors, including NF kappa B, Jun N-terminal Kinase (JNK), and various mitochondrial membrane proteins, which are likely to permit hepatocytes to survive apoptotic and oxidant stress. Previous EtOH exposure inhibits the normal regenerative induction of NF kappa B and JNK. CONCLUSIONS: These finding are consistent with the possibility that potential hepatotoxins compromise the balanced induction of toxic and trophic signals by TNF.
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- Tumor Necrosis Factor-alpha
- Signal Transduction
- Reactive Oxygen Species
- Rats, Sprague-Dawley
- Rats
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase
- NF-kappa B
- Mitogen-Activated Protein Kinases
- Mitochondria, Liver
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Necrosis Factor-alpha
- Signal Transduction
- Reactive Oxygen Species
- Rats, Sprague-Dawley
- Rats
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase
- NF-kappa B
- Mitogen-Activated Protein Kinases
- Mitochondria, Liver