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, 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 nano-switches to turn on and off proteins, similar to phosphorylation, in cells. In the cytoplasm, altered redox state can activate (e.g. MAP kinases, Nrf-2) and inhibit (e.g. phosphatases, caspases) proteins, whereas in the nucleus redox alterations can inhibit DNA binding of transcription factors (NF-kappaB, AP-1).
The consequences include promotion of expression of Antioxidants 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 pathogenesis of liver diseases.
Han D , Hanawa N , Saberi B , Kaplowitz N
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