Cholesterol oxidase from Bordetella species promotes irreversible cell apoptosis in lung adenocarcinoma by cholesterol oxidation.
Cholesterol oxidase from Bordetella species promotes irreversible cell apoptosis in lung adenocarcinoma by cholesterol oxidation.
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来自博德特氏菌属的胆固醇氧化酶通过胆固醇氧化促进肺腺癌中不可逆的细胞凋亡。
DOI：
10.1038/cddis.2014.324
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发表时间：
2014-08-14
影响因子：
9
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中科院分区：
文献类型：
--
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胆固醇氧化酶（COD）是一种催化胆固醇氧化的酶，已被应用于跟踪膜胆固醇的分布。关于COD对肿瘤细胞的影响的研究很少。在本研究中，我们提供的证据表明，COD从博德特氏菌物种（COD-B），诱导肺癌细胞在体外和体内凋亡。COD-B处理抑制Akt和ERK 1/2磷酸化的剂量和时间依赖性的方式，这是不可逆的，甚至加剧了胆固醇添加。进一步的研究表明，COD-B处理促进了活性氧（ROS）的产生，胆固醇的加入进一步提高了ROS水平。此外，COD-B处理导致JNK和p38磷酸化，Bcl-2下调，Bax上调，激活caspase-3和细胞色素C释放，这可能是对伴随胆固醇氧化的新鲜产生的过氧化氢的反应。过氧化氢酶预处理只能部分阻止COD-B诱导的事件，表明过氧化氢酶抑制H2 O2诱导的信号转导，但对参与胆固醇消耗的信号通路影响不大。我们的研究结果表明，COD-B通过降低胆固醇含量和增加ROS水平导致不可逆的细胞凋亡。此外，COD-B可能是一个有前途的候选人的一种新的抗肿瘤治疗。
Cholesterol oxidase (COD), an enzyme catalyzing the oxidation of cholesterol, has been applied to track the distribution of membrane cholesterol. Little investigations about the effect of COD on tumor cells have been performed. In the present study, we provided evidence that COD from Bordetella species (COD-B), induced apoptosis of lung cancer cells in vitro and in vivo. COD-B treatment inhibited Akt and ERK1/2 phosphorylation in dose- and time-dependent manner, which was not reversed and was even aggravated by cholesterol addition. Further investigation indicated that COD-B treatment promoted the generation of reactive oxygen species (ROS) and that cholesterol addition further elevated ROS levels. Moreover, COD-B treatment resulted in JNK and p38 phosphorylation, downregulation of Bcl-2, upregulation of Bax, activated caspase-3 and cytochrome C release, which likely responded to freshly produced hydrogen peroxide that accompanied cholesterol oxidation. Catalase pretreatment could only partially prevent COD-B-induced events, suggesting that catalase inhibited H2O2-induced signal transduction but had little effect on signal pathways involved in cholesterol depletion. Our results demonstrated that COD-B led to irreversible cell apoptosis by decreasing cholesterol content and increasing ROS level. In addition, COD-B may be a promising candidate for a novel anti-tumor therapy.
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