The future of GI and liver research: editorial perspectives. III. JNK/AP-1 regulation of hepatocyte death.
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.
Czaja
Mark J
MJ
Marion Bessin Liver Research Center and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA. czaja@aecom.yu.edu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001647:Bile Acids and Salts / Q000494:pharmacology; D035843:Biomedical Research; D016923:Cell Death; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008107:Liver Diseases / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D015427:Reperfusion Injury; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001647:Bile Acids and Salts; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases