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Poster

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Abstract

S-glutathionylation is a form of post-translational modification where glutathione forms disulfide bonds with protein cysteine residues under oxidative conditions. The process of Sglutathionylation is important because it is a reversible process, regulates enzyme activity, and may link to disease development. In this work, under physiological conditions, KEAP-1 and NRF-2 bind together as a complex. Upon oxidative stress, NRF-2 dissociates from KEAP-1 and triggers an antioxidant response. However, the dissociation mechanism was not well studied. S-glutathionylation of KEAP-1 causes dissociation of NRF-2. This result demonstrates a possible dissociation mechanism of NRF-2. Caspase 3 is a cysteine containing protein and a key enzyme in executing apoptosis in cells. The cysteine residue is required for its activity. Our results show that S-glutathionylation of the cysteine inhibits caspase 3 activity and that inhibition can be reversed by the addition of dithiothreitol (DTT). The inhibition of caspase 3 activity with GSSG and reactivation of caspase 3 activity with DTT showed a concentration dependent manner. Our work shows that the process of protein S-glutathionylation can affect cellular protein physiological functions under oxidative stress.

Publication Date

2023

The Effect of S-glutahionylation of KEAP-1/NRF-2 and Caspase 3

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Chemistry Commons

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