Prostaglandin D2 induces programmed cell death in Trypanosoma brucei bloodstream form
Prostaglandin D2 induces programmed cell death in Trypanosoma brucei bloodstream form
复制标题
DOI：
10.1038/sj.cdd.4401564
复制
发表时间：
2005-04-01
影响因子：
12.4
通讯作者：
Duszenko, M
中科院分区：
文献类型：
--
作者：
Figarella, K;Rawer, M;Duszenko, M
非洲锥虫产生一些前列腺素类，尤其是PGD（2）、PGE（2）和PGF（2 α）（Kubata等人，2000，J. Exp. 192：1327-1338），可能是为了干扰宿主的生理反应。然而，将前列腺素D-2（而不是PGE（2）或PGF（2 α））添加到培养的血流形式的锥虫中也导致细胞生长的显著抑制。基于形态学改变和使用活体染料的特异性染色方法，排除了坏死和自噬。在这里，我们报告说，在血液形式的锥虫PGD 2诱导类凋亡的程序性细胞死亡，其中包括维持质膜的完整性，磷脂酰丝氨酸暴露，线粒体膜电位的损失，核染色质凝聚和DNA降解。使用半胱天冬酶抑制剂不能阻止细胞死亡，表明该过程是半胱天冬酶非依赖性的。基于这些结果，我们认为PGD（2）诱导的程序性细胞死亡是在感染动物中观察到的群体密度调节的一部分。
African trypanosomes produce some prostanoids, especially PGD(2), PGE(2) and PGF(2 alpha) (Kubata et al. 2000, J. Exp. Med. 192: 1327-1338), probably to interfere with the host's physiological response. However, addition of prostaglandin D-2 ( but not PGE(2) or PGF(2 alpha)) to cultured bloodstream form trypanosomes led also to a significant inhibition of cell growth. Based on morphological alterations and specific staining methods using vital dyes, necrosis and autophagy were excluded. Here, we report that in bloodstream form trypanosomes PGD2 induces an apoptosis-like programmed cell death, which includes maintenance of plasma membrane integrity, phosphatidylserine exposure, loss of mitochondrial membrane potential, nuclear chromatin condensation and DNA degradation. The use of caspase inhibitors cannot prevent the cell death, indicating that the process is caspase-independent. Based on these results, we suggest that PGD(2)-induced programmed cell death is part of the population density regulation as observed in infected animals.