title: JNK potentiates TNF-stimulated necrosis by increasing the production of cytotoxic reactive oxygen species.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Juan-Jose
authors.initials: JJ
authors.lastname: Ventura
authors.forename: Patricia
authors.initials: P
authors.lastname: Cogswell
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Albert S
authors.initials: AS
authors.lastname: Baldwin
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology*; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases