Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 284, Issue 6, Pages G875-G879Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00549.2002
Keywords
mitogen-activated protein kinase; hepatocyte; c-Jun; apoptosis; tumor necrosis factor
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Funding
- NIDDK NIH HHS [DK-61498, DK-44234, R01 DK044234, R01 DK061498] Funding Source: Medline
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Activation of the JNK/activator protein-1 (AP-1)-signaling pathway is a common mediator of hepatocyte death from a variety of stimuli. Although the mechanism by which JNK or AP-1 promotes death is unknown, it results when activation of this signaling pathway is unusually prolonged. Although JNK/ AP-1 mediates TNF-induced cell death at or above the level of the mitochondria, the ability of JNK/ AP-1 to promote death from necrosis as well as apoptosis suggests that JNK/ AP-1 may induce death by several mechanisms. Recognition of JNK/ AP-1 signaling as a critical promoter of hepatocyte death raises the possibility that the therapeutic manipulation of this pathway may be effective in the treatment of human liver disease.
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