From the Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 and.
the Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, Medical University of South Carolina, Charleston, South Carolina 29425.
J Biol Chem. 2018 Nov 30;293(48):18736-18745. doi: 10.1074/jbc.TM118.003337. Epub 2018 Oct 17.
Polyamines (PAs) are indispensable polycations ubiquitous to all living cells. Among their many critical functions, PAs contribute to the oxidative balance of the cell. Beginning with studies by the Tabor laboratory in bacteria and yeast, the requirement for PAs as protectors against oxygen radical-mediated damage has been well established in many organisms, including mammals. However, PAs also serve as substrates for oxidation reactions that produce hydrogen peroxide (HO) both intra- and extracellularly. As intracellular concentrations of PAs can reach millimolar concentrations, the HO amounts produced through their catabolism, coupled with a reduction in protective PAs, are sufficient to cause the oxidative damage associated with many pathologies, including cancer. Thus, the maintenance of intracellular polyamine homeostasis may ultimately contribute to the maintenance of oxidative homeostasis. Again, pioneering studies by Tabor and colleagues led the way in first identifying spermine oxidase in They also first purified the extracellular bovine serum amine oxidase and elucidated the products of its oxidation of primary amine groups of PAs when included in culture medium. These investigations formed the foundation for many polyamine-related studies and experimental procedures still performed today. This Minireview will summarize key innovative studies regarding PAs and oxidative damage, starting with those from the Tabor laboratory and including the most recent advances, with a focus on mammalian systems.
多胺(PAs)是所有活细胞中普遍存在的必不可少的多阳离子。在它们的许多关键功能中,PAs 有助于细胞的氧化平衡。从 Tabor 实验室在细菌和酵母中的研究开始,PAs 作为保护细胞免受氧自由基介导的损伤的物质,已经在许多生物体中得到了很好的证实,包括哺乳动物。然而,PAs 也可以作为氧化反应的底物,这些反应在细胞内和细胞外都会产生过氧化氢(HO)。由于细胞内 PAs 的浓度可以达到毫摩尔浓度,因此通过其代谢产生的 HO 量,加上保护性 PAs 的减少,足以导致与许多病理学相关的氧化损伤,包括癌症。因此,维持细胞内多胺的稳态最终可能有助于维持氧化的稳态。同样,Tabor 和他的同事们的开创性研究率先在 中鉴定了精脒氧化酶;他们还首次纯化了牛血清胺氧化酶,并阐明了其在包含在培养基中的 PAs 的伯胺基团氧化时的产物。这些研究为许多与多胺相关的研究和实验程序奠定了基础,这些程序至今仍在进行。这篇综述将总结关于 PAs 和氧化损伤的关键创新研究,从 Tabor 实验室的研究开始,并包括最新的进展,重点是哺乳动物系统。