Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Brisbane 4111, Australia.
Department of Pathology and Biological Responses, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan.
Biomolecules. 2022 Sep 13;12(9):1292. doi: 10.3390/biom12091292.
Glutathione--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.
谷胱甘肽转移酶（GSTs）在与多种蛋白质相互作用方面具有高度的混杂性，导致其具有多种功能。除了与多药耐药相关蛋白-1（MRP1）的经典解毒作用外，最近的研究表明 GSTs 在细胞一氧化氮（NO）代谢中的作用。血管舒张通常通过 NO 与可溶性鸟苷酸环化酶的相互作用来诱导。GSTs 将有机硝酸盐（如硝化甘油）生物转化为 NO 的能力可以显著调节血管舒张，这种作用可以被特定的 GST 抑制剂所阻止。最近，其他结构不同的前药通过 GST 介导的催化作用产生 NO，已被开发为抗癌药物，也表明 GSTs 作为药物开发的合适靶点具有潜力。进一步研究 GST 生物化学可以增强我们对 NO 代谢的理解，并为临床应用产生新的创新血管扩张剂。
