Wittgen Hanneke G M, van Kempen Léon C L T
Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Melanoma Res. 2007 Dec;17(6):400-9. doi: 10.1097/CMR.0b013e3282f1d312.
Oxidative phosphorylation in the mitochondria is an important energy-producing process for eukaryotic cells, but this process can also result in producing potentially cell-damaging side products. Oxygen is the final proton acceptor in this cascade of electron/proton transfer and results in harmless water. The electron transfer, however, is not completely efficient and results in the production of reactive oxygen species (ROS). Low amounts of these ROS are important for cellular-signalling pathways. Excessive ROS, however, can induce cell damage that can culminate in cell death. Therefore, the cell has developed an antioxidant network to scavenge excessively produced ROS. In general, the balance between the production and scavenging of ROS leads to homeostasis. Disturbance of this equilibrium can alter normal cellular processes; it often occurs in tumour cells. In this review, the role of ROS in cutaneous melanoma development and progression is described. Cutaneous melanoma arises from epidermal melanocytes in skin, which is a relatively hypoxic tissue. ROS are generated as a result of increased metabolism of transformed cells, immune reaction against the developing tumour, ultraviolet radiation, melanin production and an altered antioxidant system. Knowledge of the role of ROS in melanoma development and the mechanisms that alleviate oxidative stress can aid in the development of better antimelanoma therapies.
线粒体中的氧化磷酸化是真核细胞重要的能量产生过程，但该过程也可能产生具有潜在细胞损伤性的副产物。氧气是这一系列电子/质子转移过程中的最终质子受体，会生成无害的水。然而，电子转移并不完全高效，会产生活性氧（ROS）。少量的这些ROS对细胞信号通路很重要。然而，过量的ROS会诱导细胞损伤，最终导致细胞死亡。因此，细胞形成了一个抗氧化网络来清除过量产生的ROS。一般来说，ROS产生与清除之间的平衡导致内稳态。这种平衡的破坏会改变正常的细胞过程；它经常发生在肿瘤细胞中。在这篇综述中，描述了ROS在皮肤黑色素瘤发生和发展中的作用。皮肤黑色素瘤起源于皮肤中的表皮黑素细胞，皮肤是一个相对缺氧的组织。ROS是由转化细胞代谢增加、针对正在发展的肿瘤的免疫反应、紫外线辐射、黑色素生成以及抗氧化系统改变所产生的。了解ROS在黑色素瘤发生中的作用以及减轻氧化应激的机制有助于开发更好的抗黑色素瘤疗法。
