Glutathione-S-Transferases as Potential Targets for Modulation of Nitric Oxide-Mediated Vasodilation

Abstract

Glutathione-S-transferases (GSTs) are highly promiscuous in terms of their interactions with multiple proteins, leading to various functions. In addition to their classical detoxification roles with multi-drug resistance-related protein-1 (MRP1), more recent studies have indicated the role of GSTs in cellular nitric oxide (NO) metabolism. Vasodilation is classically induced by NO through its interaction with soluble guanylate cyclase. The ability of GSTs to biotransform organic nitrates such as nitroglycerin for NO generation can markedly modulate vasodilation, with this effect being prevented by specific GST inhibitors. Recently, other structurally distinct pro-drugs that generate NO via GST-mediated catalysis have been developed as anti-cancer agents and also indicate the potential of GSTs as suitable targets for pharmaceutical development. Further studies investigating GST biochemistry could enhance our understanding of NO metabolism and lead to the generation of novel and innovative vasodilators for clinical use.