Role of oxygen radicals generated by NADPH oxidase in apoptosis induced in human leukemia cells
Role of oxygen radicals generated by NADPH oxidase in apoptosis induced in human leukemia cells
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DOI：
10.1172/jci3437
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发表时间：
1998-12-01
影响因子：
15.9
通讯作者：
Pommier, Y
中科院分区：
文献类型：
--
作者：
Hiraoka, W;Vazquez, N;Pommier, Y
我们使用了一种人类白血病细胞系，在同源重组敲除吞噬细胞呼吸爆发氧化酶细胞色素b-558的gp91-phox亚基后，模拟慢性肉芽肿病（X-CGD）来研究氧自由基在细胞凋亡中的作用。喜树碱（CPT）是一种拓扑异构酶I抑制剂，在PLB-985细胞中诱导的凋亡明显多于X-CGD细胞。中性粒细胞分化后CPT敏感性增强，单核细胞分化后CPT敏感性下降。在其他凋亡诱导剂（包括etopo苷、紫外线辐射、电离辐射、过氧化氢或7-羟基孢素）处理后，两种细胞系之间没有观察到差异。两种细胞系在粒细胞分化后，CPT仍然诱导细胞凋亡，这表明在完全分化和生长受阻的细胞中，CPT与复制无关。吡咯烷二硫代氨基甲酸酯（NF-kappa B的抗氧化抑制剂）和过氧化氢酶部分抑制cpt诱导的粒细胞分化PLB-985细胞的DNA断裂，但对X-CGD细胞没有影响。流式细胞术分析显示，cpt处理的PLB-985细胞产生了活性氧中间体。这些数据表明，NADPH氧化酶产生的氧自由基可能直接或间接地参与了cpt诱导的人白血病和中性粒细胞分化细胞的凋亡。
We have used a human leukemia cell line that, after homologous recombination knockout of the gp91-phox subunit of the phagocyte respiratory-burst oxidase cytochrome b-558, mimics chronic granulomatous disease (X-CGD) to study the role of oxygen radicals in apoptosis. Camptothecin (CPT), a topoisomerase I inhibitor, induced significantly more apoptosis in PLB-985 cells than in X-CGD cells. Sensitivity to CPT was enhanced after neutrophilic differentiation, but was lost after monocytic differentiation. No difference between the two cell lines was observed after treatment with other apoptosis inducers, including etoposide, ultraviolet radiation, ionizing radiation, hydrogen peroxide, or 7-hydroxystaurosporine. After granulocytic differentiation of both cell lines, CPT still induced apoptosis, suggesting independence from replication in fully differentiated and growth-arrested cells. Pyrrolidine dithiocarbamate (an antioxidant inhibitor of NF-kappa B) and catalase partially inhibited CPT-induced DNA fragmentation in granulocytic-differentiated PLB-985 cells, but had no effect in X-CGD cells. Flow cytometry analysis revealed that reactive oxygen intermediates were generated in CPT-treated PLB-985 cells. These data indicate that oxygen radicals generated by NADPH oxidase may contribute directly or indirectly to CPT-induced apoptosis in human leukemia and in neutrophilic-differentiated cells.