JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species
Howard Hughes Medical Institute and Program in Molecular Medicine
Animals; Cell Death; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; Mice; Mitogen-Activated Protein Kinase Kinases; *Reactive Oxygen Species; Tumor Necrosis Factor-alpha
Life Sciences | Medicine and Health Sciences
The c-Jun NH(2)-terminal kinase (JNK) has been implicated in both cell death and survival responses to different stimuli. Here we reexamine the function of JNK in tumor necrosis factor (TNF)-stimulated cell death using fibroblasts isolated from wild-type, Mkk4(-/-) Mkk7(-/-), and Jnk1(-/-) Jnk2(-/-) mice. We demonstrate that JNK can act to suppress TNF-stimulated apoptosis. However, we find that JNK can also potentiate TNF-stimulated necrosis by increasing the production of reactive oxygen species (ROS). Together, these data indicate that JNK can shift the balance of TNF-stimulated cell death from apoptosis to necrosis. Increased necrosis may represent a contributing factor in stress-induced inflammatory responses mediated by JNK.
DOI of Published Version
Genes Dev. 2004 Dec 1;18(23):2905-15. Epub 2004 Nov 15. Link to article on publisher's site
Genes and development
Ventura, Juan-Jose; Cogswell, Patricia C.; Flavell, Richard A.; Baldwin, Albert S. Jr.; and Davis, Roger J., "JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species" (2004). Open Access Articles. 576.