JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species

AUTOR(ES)

Ventura, Juan-Jose

FONTE

Cold Spring Harbor Laboratory Press

RESUMO

The c-Jun NH2-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.

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