TY - JOUR
T1 - Mechanisms of liver injury. III. Role of glutathione redox status in liver injury
AU - Han, Derick
AU - Hanawa, Naoko
AU - Saberi, Behnam
AU - Kaplowitz, Neil
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006
Y1 - 2006
N2 - GSH is the most abundant redox molecule in cells and thus the most important determinant of cellular redox status. Thiols in proteins can undergo a wide range of reversible redox modifications (e.g., S-glutathionylation, S-nitrosylation, and disulfide formation) during times of increased exposure to reactive oxygen and nitrogen species, which can affect protein activity. These reversible thiol modifications regulated by GSH may be nanoswitches to turn on and off proteins, similar to phosphorylation, in cells. In the cytoplasm, an altered redox state can activate (e.g., MAPKs and NF-E2-related factor-2) and inhibit (e.g., phosphatases and caspases) proteins, whereas in the nucleus, redox alterations can inhibit DNA binding of transcription factors (e.g., NF-κB and activator protein-1). The consequences include the promotion of expression of antioxidant genes and alterations of hepatocyte survival as well as the balance between necrotic versus apoptotic cell death. Therefore, the understanding of the redox regulation of proteins may have important clinical ramifications in understanding the pathogenesis of liver diseases.
AB - GSH is the most abundant redox molecule in cells and thus the most important determinant of cellular redox status. Thiols in proteins can undergo a wide range of reversible redox modifications (e.g., S-glutathionylation, S-nitrosylation, and disulfide formation) during times of increased exposure to reactive oxygen and nitrogen species, which can affect protein activity. These reversible thiol modifications regulated by GSH may be nanoswitches to turn on and off proteins, similar to phosphorylation, in cells. In the cytoplasm, an altered redox state can activate (e.g., MAPKs and NF-E2-related factor-2) and inhibit (e.g., phosphatases and caspases) proteins, whereas in the nucleus, redox alterations can inhibit DNA binding of transcription factors (e.g., NF-κB and activator protein-1). The consequences include the promotion of expression of antioxidant genes and alterations of hepatocyte survival as well as the balance between necrotic versus apoptotic cell death. Therefore, the understanding of the redox regulation of proteins may have important clinical ramifications in understanding the pathogenesis of liver diseases.
KW - Disulfide
KW - S-glutathionylation
KW - Thiol
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U2 - 10.1152/ajpgi.00001.2006
DO - 10.1152/ajpgi.00001.2006
M3 - Article
C2 - 16500922
AN - SCOPUS:33745791542
VL - 291
SP - G1-G7
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 1
ER -