Miltefosine-unresponsive Leishmania donovani has a greater ability than miltefosine-responsive L. donovani to resist reactive oxygen species
Miltefosine-unresponsive Leishmania donovani has a greater ability than miltefosine-responsive L. donovani to resist reactive oxygen species
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DOI：
10.1111/febs.12449
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发表时间：
2013-10-01
期刊：
影响因子：
5.4
通讯作者：
Dubey, Vikash K.
中科院分区：
文献类型：
--
作者：
Das, Mousumi;Saudagar, Prakash;Dubey, Vikash K.
利什曼原虫对米替福辛的耐药性是一个令人担忧的问题，米替福辛是唯一可用的口服药物。我们分析了米替福辛无反应和米替福辛反应利什曼尼亚多诺瓦尼的全局基因表达谱，以了解米替福辛耐药性中涉及的各种代谢过程。微阵列数据清楚地表明氧化代谢在米替福辛耐药中的作用。此外，荧光显微镜实验表明，对米替福辛无反应的杜氏乳杆菌可以抵抗活性氧的积累以及随后导致细胞凋亡的线粒体膜损伤。相反，在米替福辛反应性杜氏乳杆菌中，活性氧的积累会导致细胞凋亡。总体而言，这项研究为 L.donovani 中的米替福辛耐药性提供了基本见解。数据库微阵列数据已存储在基因表达综合数据库中，登录号为 GSE45496
Resistance of Leishmania parasites to miltefosine, which is only available oral drug, is a great concern. We have analyzed global gene expression profiles of miltefosine-unresponsive and miltefosine-responsive Leishmaniadonovani in order to understand the various metabolic processes involved in miltefosine drug resistance. The microarray data clearly indicated a role of oxidative metabolism in miltefosine resistance. Furthermore, fluorescence microscopy experiments suggested that miltefosine-unresponsive L.donovani resists the accumulation of reactive oxygen species and subsequent mitochondrial membrane damage leading to apoptotic death. In contrast, in miltefosine-responsive L.donovani, the accumulation of reactive oxygen species causes apoptotic death. Overall, this study provides fundamental insights into miltefosine resistance in L.donovani.DatabaseThe microarray data have been deposited in the Gene Expression Omnibus database under the accession number GSE45496