Glutathione and cysteine-rich proteins (GSH/CRPs)

Glutathione and cysteine-rich proteins (CRPs) constitute the primary endogenous thiol-based defense system against oxidative stress and electrophilic insult. Glutathione, a tripeptide, is the most abundant non-protein thiol in the cell, while CRPs like metallothioneins provide additional buffering capacity through their high cysteine content (Gadd, 2010). This collective target is a focal point in the mechanism of action for electrophilic compounds such as phenethyl isothiocyanate (PEITC), which covalently modifies these thiols to induce selective apoptosis in cancer cells by overwhelming their redox capacity (Amornsil & Trachootham, 2020). Additionally, these molecules play a critical role in the detoxification of heavy metals and platinum-based chemotherapeutics like cisplatin. While targeting this pool can be therapeutically beneficial in oncology, its upregulation is a major driver of drug resistance, as it allows cells to sequester and inactivate therapeutic agents (Kuroda & Ueda, 2010). Consequently, monitoring the levels and redox state of these thiols serves as a vital indicator of cellular health and therapeutic response.

Other names

Cellular thiol poolEndogenous nucleophilesRedox-active thiolsNon-protein and protein thiolsThiol-containing molecules

Covalent modification and depletion of cellular thiol groups, leading to the exhaustion of antioxidant capacity and induction of reactive oxygen species (ROS)-mediated apoptosis.