Kayanoki Y, Fujii J, Islam K N, Suzuki K, Kawata S, Matsuzawa Y, Taniguchi N
Department of Biochemistry, Osaka University Medical School.
J Biochem. 1996 Apr;119(4):817-22. doi: 10.1093/oxfordjournals.jbchem.a021313.
Selenium-dependent glutathione peroxidase (GPx) plays a protective role in oxidative stress-induced apoptosis. In this study, we demonstrated that MDBK cells, a bovine renal epithelial cell line, exhibited internucleosomal DNA fragmentation characteristic of apoptotic cell death under selenium-deficient conditions with lower doses of hydrogen peroxide (H2O2) than under selenium-supplemented ones. This was due to a decreased amount of GPx in the cells under selenium-deficient conditions, because other antioxidative enzyme activities were not affected by the selenium supplementation. Cumene hydroperoxide also induced DNA fragmentation in selenium-deficient cells but no ladder formation was observed. Flow cytometric analysis showed that selenium-deficient cells were less capable of scavenging intracellular peroxides after exposure to exogenous H2O2 than selenium-supplemented ones. In contrast, there was no difference in viability between selenium-supplemented and non-supplemented cells in cell survival after exposure to menadione, which activates the electron transport system and increases intracellular superoxide radicals. Clofibrate, a peroxisomal proliferator and an inducer of catalase (CAT), partially protected both Se-deficient and Se-supplemented cells from exogenous H202. We concluded that selenium-deficient cells were more easily brought to apoptotic cell death by peroxides, but not by superoxide radicals, than selenium-supplemented ones and that CAT could compensate for the depletion of GPx to a certain degree by scavenging H2O2.
硒依赖型谷胱甘肽过氧化物酶（GPx）在氧化应激诱导的细胞凋亡中发挥保护作用。在本研究中，我们证明了牛肾上皮细胞系MDBK细胞在缺硒条件下，与补硒条件相比，在较低剂量过氧化氢（H2O2）作用下表现出凋亡细胞死亡特征性的核小体间DNA片段化。这是由于缺硒条件下细胞中GPx含量降低，因为其他抗氧化酶活性不受补硒影响。异丙苯过氧化氢也诱导缺硒细胞中的DNA片段化，但未观察到梯状条带形成。流式细胞术分析表明，缺硒细胞在暴露于外源性H2O2后清除细胞内过氧化物的能力低于补硒细胞。相反，在暴露于甲萘醌（其激活电子传递系统并增加细胞内超氧自由基）后，补硒细胞和未补硒细胞在细胞存活能力方面没有差异。氯贝丁酯是一种过氧化物酶体增殖剂和过氧化氢酶（CAT）诱导剂，可部分保护缺硒和补硒细胞免受外源性H2O2的损伤。我们得出结论，与补硒细胞相比，缺硒细胞更容易因过氧化物而非超氧自由基导致凋亡细胞死亡，并且CAT可以通过清除H2O2在一定程度上补偿GPx的消耗。
