Ivanovas Boris, Zerweck Alf, Bauer Georg
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Germany.
Anticancer Res. 2002 Mar-Apr;22(2A):841-56.
This paper defines selective and nonselective apoptosis induction in transformed and nontransformed fibroblasts by extracellular reactive oxygen and nitrogen species (ROS and RNS). Superoxide anions do not exhibit direct apoptosis inducing potential, whereas their dismutation product hydrogen peroxide induces apoptosis nonselectively in transformed and nontransformed fibroblasts. Myeloperoxidase converts hydrogen peroxide into the selective apoptosis mediator HOCl, which interacts with transformed target cell-derived superoxide anions and generates apoptosis-inducing hydroxyl radicals. Nitric oxide does not induce apoptosis directly in fibroblasts. However, interaction of nitric oxide with transformed cell-derived superoxide anions leads to the generation of the ultimate apoptosis inducer, peroxynitrite. Peroxynitrite by itself does not discriminate between transformed and nontransformed cells. The direction of generation of apoptosis inducing ROS and RNS to the site of superoxide anion production has relevance for the selectivity of ROS and RNS-based natural antitumor systems, as extracellular superoxide anion generation represents a hallmark of the transformed state.
本文定义了细胞外活性氧和氮物种（ROS和RNS）在转化和未转化的成纤维细胞中诱导选择性和非选择性凋亡的情况。超氧阴离子不具有直接诱导凋亡的潜力，而其歧化产物过氧化氢在转化和未转化的成纤维细胞中均非选择性地诱导凋亡。髓过氧化物酶将过氧化氢转化为选择性凋亡介质次氯酸，次氯酸与转化的靶细胞衍生的超氧阴离子相互作用并产生诱导凋亡的羟基自由基。一氧化氮本身不会直接在成纤维细胞中诱导凋亡。然而，一氧化氮与转化细胞衍生的超氧阴离子相互作用会导致最终凋亡诱导剂过氧亚硝酸盐的产生。过氧亚硝酸盐本身不会区分转化细胞和未转化细胞。诱导凋亡的ROS和RNS向超氧阴离子产生部位的生成方向与基于ROS和RNS的天然抗肿瘤系统的选择性相关，因为细胞外超氧阴离子的产生是转化状态的一个标志。
