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Redox regulation of hepatocyte apoptosis
Author(s) -
GarciaRuiz Carmen,
FernándezCheca José C
Publication year - 2007
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2006.04644.x
Subject(s) - medicine , hepatocyte , apoptosis , redox , microbiology and biotechnology , cancer research , biochemistry , in vitro , biology , materials science , metallurgy
Cell death can be regulated by the sensitivity of proteins with a functional role in death pathways to redox environment. The antioxidant glutathione (GSH) regulates cell death pathways by modulating the redox state of specific thiol residues of target proteins including transcription factors, stress kinases and caspases, which participate in tumor necrosis factor (TNF)‐induced apoptosis. The TNF signals, upon its binding to its type 1 receptor, two simultaneous pathways with opposing functions, promoting cell survival through NF‐κB activation or cell death through mitochondria. As a consequence, hepatocytes are resistant to TNF unless the survival arm is neutralized, therefore, rendering hepatocytes sensitive to TNF. Cytosol GSH regulates TNF hepatocyte apoptosis by modulating caspase 8 activation or NF‐κB‐dependent gene expression. However, mitochondrial GSH controls hepatocyte susceptibility to TNF through modulation of reactive oxygen species, without inactivation of NF‐κB‐dependent survival pathways. So, understanding the role of mitochondrial reactive oxygen species in TNF‐induced hepatocyte death may have broad implications in the pathogenesis of acute and chronic liver diseases.