Abstract
Apoptosis is a prominent feature of liver diseases. Causative factors such as alcohol, viruses, toxic bile acids, fatty acids, drugs, and immune response, can induce apoptotic cell death via membrane receptors and intracellular stress. Apoptotic signaling network, including membrane death receptor-mediated cascade, reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress, lysosomal permeabilization, and mitochondrial dysfunction, is intermixed each other, but one mechanism may dominate at a particular stage. Mechanisms of hepatic apoptosis are complicated by multiple signaling pathways. The progression of liver disease is affected by the balance between apoptotic and antiapoptotic capabilities. Therapeutic options of liver injury are impacted by the clear understanding toward mechanisms of hepatic apoptosis.
Highlights
Introduction of Hepatic ApoptosisLiver injury can be caused by different stimuli such as alcohol intake, viral infection, cholestasis, steatosis, drug abuse, and autoimmunity.[1,2,3,4,5,6] Genetic variability is interacted with environmental factors, which makes liver damage in a variety of Etiology and Mechanisms of Hepatic ApoptosisViruses
TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis could be switched into regulated necrosis in human HT29 and HepG2 cells under acidic extracellular condition
The role of TRAIL as inducer of necroptosis had been shown in a mouse model of Con A-induced hepatitis, where death of hepatocytes was dependent on TRAIL and natural killer T cells.[128]
Summary
Apoptosis is a prominent feature of liver diseases. Causative factors such as alcohol, viruses, toxic bile acids, fatty acids, drugs, and immune response, can induce apoptotic cell death via membrane receptors and intracellular stress. Apoptotic signaling network, including membrane death receptor-mediated cascade, reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress, lysosomal permeabilization, and mitochondrial dysfunction, is intermixed each other, but one mechanism may dominate at a particular stage. Therapeutic options of liver injury are impacted by the clear understanding toward mechanisms of hepatic apoptosis. Apoptosis is a typical pathological feature of liver diseases. Interventions for hepatic apoptosis alleviate liver injury as demonstrated by pre-clinical models and clinical trials. The regulation of hepatic apoptosis affects the progression of liver diseases
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