Matsunaga T, Kudo J, Takahashi K, Dohmen K, Hayashida K, Okamura S, Ishibashi H, Niho Y
The First Department of Internal Medicine, Kyushu University, Fukuoka, Japan.
Leuk Lymphoma. 1996 Feb;20(5-6):487-94. doi: 10.3109/10428199609052434.
We previously demonstrated that the mitochondrial NADH dehydrogenase subunit 2 (ND2) gene was overexpressed in human acute myelogenous leukemia (AML) cells. Since this finding suggested that ND2 gene expression was related to myeloid differentiation, we here investigated the effects of rotenone, a specific NADH dehydrogenase inhibitor, on HL-60 cell growth, differentiation and death. Fifty nM rotenone inhibited the growth of HL-60 cells and caused an increase in the cell population in the G(2) +M phase. In the quantitative comparison of myeloid antigen, the expression of CD13 and CD38 were relatively increased in the rotenone-treated cells. These findings suggest that the inhibition of NADH dehydrogenase changes the cell cycle and induces some specific surface antigens of HL-60 cells. On the other hand, the expression of ND2 gene remained unchanged after the rotenone treatment, suggesting the rotenone-mediated mitochondrial inhibition did not affect the mitochondrial gene expression. Five mu M rotenone strongly inhibited the cellular proliferation. Electron microscopy and an electrophoretic analysis of DNA showed that the majority of the HL-60 cells were induced into typical apoptosis within 24-48 hours. On the basis of this and other studies, we believe that mitochondrial function is directly involved in both cellular differentiation and apoptotic cell death.
我们先前证明，线粒体NADH脱氢酶亚基2（ND2）基因在人类急性髓性白血病（AML）细胞中过表达。由于这一发现表明ND2基因表达与髓系分化有关，我们在此研究了鱼藤酮（一种特异性NADH脱氢酶抑制剂）对HL-60细胞生长、分化和死亡的影响。50 nM鱼藤酮抑制HL-60细胞的生长，并导致G(2)+M期细胞数量增加。在髓系抗原的定量比较中，鱼藤酮处理的细胞中CD13和CD38的表达相对增加。这些发现表明，NADH脱氢酶的抑制改变了细胞周期，并诱导了HL-60细胞的一些特异性表面抗原。另一方面，鱼藤酮处理后ND2基因的表达保持不变，这表明鱼藤酮介导的线粒体抑制并未影响线粒体基因表达。5 μM鱼藤酮强烈抑制细胞增殖。电子显微镜和DNA电泳分析表明，大多数HL-60细胞在24-48小时内被诱导进入典型的凋亡状态。基于这项研究和其他研究，我们认为线粒体功能直接参与细胞分化和凋亡性细胞死亡。
