TY - JOUR
T1 - Induction and regulation of hepatocyte apoptosis by oxidative stress
AU - Czaja, Mark J.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2002/10
Y1 - 2002/10
N2 - Reactive oxygen intermediates (ROI) have been implicated in the induction of hepatocyte apoptosis that results from a variety of forms of liver injury. Exogenous oxidants induce hepatocyte apoptosis and may mediate death during inflammatory liver injury. Lethal levels of intracellularly generated ROI resulting from hepatotoxin metabolism, or the induction of enzymes in the cytochrome P450 family, are also important inducers of apoptosis. In addition, ROI production may mediate death from a number of diverse factors, including tumor necrosis factor-α, bile acids, ischemia, and transforming growth factor-β. Oxidants alter many redox-sensitive cellular signaling pathways, including mitogen-activated protein kinases and transcription factors such as activator protein-1 and nuclear factor-κB. The mechanisms of oxidant-induced hepatocyte apoptosis remain unclear, but probably involve effects on cell signaling, as well as direct chemical interactions. The delineation of stimulus-specific mechanisms of oxidant-dependent hepatocyte apoptosis is important to the design of effective therapies for a number of forms of liver injury.
AB - Reactive oxygen intermediates (ROI) have been implicated in the induction of hepatocyte apoptosis that results from a variety of forms of liver injury. Exogenous oxidants induce hepatocyte apoptosis and may mediate death during inflammatory liver injury. Lethal levels of intracellularly generated ROI resulting from hepatotoxin metabolism, or the induction of enzymes in the cytochrome P450 family, are also important inducers of apoptosis. In addition, ROI production may mediate death from a number of diverse factors, including tumor necrosis factor-α, bile acids, ischemia, and transforming growth factor-β. Oxidants alter many redox-sensitive cellular signaling pathways, including mitogen-activated protein kinases and transcription factors such as activator protein-1 and nuclear factor-κB. The mechanisms of oxidant-induced hepatocyte apoptosis remain unclear, but probably involve effects on cell signaling, as well as direct chemical interactions. The delineation of stimulus-specific mechanisms of oxidant-dependent hepatocyte apoptosis is important to the design of effective therapies for a number of forms of liver injury.
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U2 - 10.1089/152308602760598909
DO - 10.1089/152308602760598909
M3 - Review article
C2 - 12470503
AN - SCOPUS:0036775096
VL - 4
SP - 759
EP - 767
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 5
ER -