Engelmann I, Dormann S, Saran M, Bauer G
Abteilung Virologie, Institut für Medinische Mikrobiologie und Hygiene, Universität Freiburg, Germany.
Redox Rep. 2000;5(4):207-14. doi: 10.1179/135100000101535762.
Myeloperoxidase induces apoptosis in src- or raxs-transformed fibroblasts, but not in parental nontransformed fibroblasts. This selectivity seems to be based on superoxide anion production by transformed cells, a recently described characteristic feature of transformed cells. Myeloperoxidase-mediated apoptosis induction is inhibited by SOD, catalase, 4-aminobenzoyl hydrazide, taurine and DMSO. This pattern of inhibition allows us to conclude that transformed cell derived superoxide anions dismutate to hydrogen peroxide, which fosters HOCl formation by myeloperoxidase. Hydrogen peroxide formation thereby is the rate-limiting step and depends on the cell density. In a second step, HOCl interacts with superoxide anions to yield the highly reactive apoptosis inducing hydroxyl radical. This conclusion was verified through selective apoptosis induction in transformed cells by direct addition of HOCl, which was also inhibited by SOD and DMSO. Our findings demonstrate a specific interplay between target cell derived superoxide anions and MPO during selective apoptosis induction.
髓过氧化物酶可诱导src或ras转化的成纤维细胞发生凋亡，但对亲代未转化的成纤维细胞无此作用。这种选择性似乎基于转化细胞产生的超氧阴离子，这是最近描述的转化细胞的一个特征。超氧化物歧化酶（SOD）、过氧化氢酶、4-氨基苯甲酰肼、牛磺酸和二甲基亚砜（DMSO）可抑制髓过氧化物酶介导的凋亡诱导。这种抑制模式使我们得出结论，转化细胞衍生的超氧阴离子歧化为过氧化氢，而过氧化氢促进髓过氧化物酶形成次氯酸（HOCl）。因此，过氧化氢的形成是限速步骤，且取决于细胞密度。在第二步中，HOCl与超氧阴离子相互作用产生高反应性的诱导凋亡的羟基自由基。通过直接添加HOCl在转化细胞中诱导选择性凋亡也得到了验证，其同样受到SOD和DMSO的抑制。我们的研究结果表明，在选择性凋亡诱导过程中，靶细胞衍生的超氧阴离子与髓过氧化物酶之间存在特定的相互作用。
