Mechanisms of liver cell injury

Liver cell death is triggered by a number of insults arising from the exter nal environment or from within the cell. These insults may engage cell surf ace receptors with death domaines leading to a proteolytic cascade involvin g initiator and executioner caspases and an apoptotic demise. Alternatively , the insults may profoundly disrupt mitochondrial function and result in l oss of homeostasis accompanied by activation of hydrolases and a necrotic o r lyric demise. The distinction between apoptotic and necrotic cell death h as become blurred recently by the recognition that the same stimuli can ind uce either form of cell, death as well as caspase independent apoptosis, Mi tochondria play a key role in the shape of cell death; selective release of mediators amplifies the apoptosis program and profound loss of mitochondri al function leads to necrosis, Reactive oxygen metabolites and nitric oxide participate as intitiating factors and modulators. The extensive knowledge gained in recent years about the mechanisms of cell death will undoubtedly lead to new and exciting advances in the prevention and treatment of liver diseases. Important targets include death receptors, death signaling mecha nisms, the mitochondrial permeability transition and approaches which selec tively inhibit or activate cell death in parenchymal versus nonparenchymal cells.