Czaja Mark J
Marion Bessin Liver Research Center and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Am J Physiol Gastrointest Liver Physiol. 2003 Jun;284(6):G875-9. doi: 10.1152/ajpgi.00549.2002.
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.
JNK/激活蛋白-1（AP-1）信号通路的激活是多种刺激导致肝细胞死亡的常见介质。尽管JNK或AP-1促进细胞死亡的机制尚不清楚，但当该信号通路的激活异常延长时就会发生细胞死亡。虽然JNK/AP-1在线粒体水平或以上介导肿瘤坏死因子（TNF）诱导的细胞死亡，但JNK/AP-1促进坏死和凋亡性细胞死亡的能力表明，JNK/AP-1可能通过多种机制诱导细胞死亡。认识到JNK/AP-1信号是肝细胞死亡的关键促进因素，这增加了对该信号通路进行治疗性调控可能有效治疗人类肝脏疾病的可能性。
