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.
Marion Bessin Liver Research Center and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA. czaja@aecom.yu.edu
Mark J
MJ
Czaja
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