Glutathione-dependent redox system (GSH system) (GSH system)

The glutathione-dependent redox system is a fundamental antioxidant network essential for maintaining cellular redox homeostasis and protecting against oxidative stress (NCBI, 2023). It comprises the tripeptide glutathione (GSH) and several key enzymes, including glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) (StatPearls, 2023). This system functions by neutralizing reactive oxygen species (ROS) and detoxifying electrophilic compounds, thereby preventing damage to DNA, proteins, and lipids (PubMed, 2021). In oncology, many tumors overexpress components of this system to survive high levels of oxidative stress and resist chemotherapy, leading to the development of inhibitors like buthionine sulfoximine (BSO) or ferroptosis-inducing agents that target GPx4 (Nature, 2020). In contrast, for conditions like neurodegeneration and chronic inflammation, therapeutic strategies often focus on augmenting the system using precursors like N-acetylcysteine to bolster cellular defenses against oxidative injury (PubMed, 2022).

Other names

Glutathione redox systemGSH/GSSG systemGlutathione antioxidant systemReactive oxygen species / glutathione-dependent redox system

Modulation of glutathione levels or activity of glutathione-dependent enzymes to alter cellular redox state, including GSH replenishment, GSH depletion, and inhibition of enzymes like GPx4 or GST.