Imbalanced expression of Bcl-xL and Bax in platelets treated with plasma from immune thrombocytopenia
Imbalanced expression of Bcl-xL and Bax in platelets treated with plasma from immune thrombocytopenia
复制标题
免疫性血小板减少症血浆处理后的血小板中 Bcl-xL 和 Bax 表达失衡
DOI：
10.1007/s12026-015-8760-z
复制
发表时间：
2016-04-01
影响因子：
4.4
通讯作者：
Zeng, Lingyu
中科院分区：
文献类型：
--
作者：
Qiao, Jianlin;Liu, Yun;Zeng, Lingyu
免疫性血小板减少症是一种异质性自身免疫性疾病，其特征是血小板破坏加速和血小板生成受损。Bcl-xL和Bax在凋亡过程中起相反的调节作用，Bcl-xL对细胞存活起作用，Bax对细胞凋亡起作用。由于Bcl-xL或Bax在血小板凋亡调控中的重要作用，因此Bcl-xL或Bax是否参与ITP的发病机制仍不清楚。本研究的目的是评估Bcl-xL和Bax在ITP血浆处理的血小板中的表达谱。用来自20名活动性ITP患者或10名年龄和性别匹配的对照的血浆处理正常洗涤的血小板以模拟ITP体内环境。流式细胞术检测线粒体去极化、血小板凋亡和活化。实时荧光定量PCR和Western blot检测Bcl-xL、Bax和caspase-3的表达。我们的研究结果表明，与对照组相比，ITP血浆治疗后血小板中的线粒体去极化、血小板凋亡和活化增加。此外，Bcl-xL表达减少，Bax表达增加，caspase-3活性升高。ITP血浆处理后血小板中Bcl-xL与Bax表达呈负相关。结论：Bcl-xL和Bax的失衡表达可能与ITP血小板凋亡有关，靶向治疗可能是治疗ITP的新途径。
Immune thrombocytopenia is a heterogeneous autoimmune disease, characterized by accelerated platelet destruction and impaired platelet production. Bcl-xL and Bax play an opposite role in the regulation of apoptotic process with Bcl-xL for cell survival and Bax for cell apoptosis. Given the critical roles in the regulation of platelet apoptosis, whether Bcl-xL or Bax was involved in the pathogenesis of ITP remains unknown. The aim of this study is to evaluate the expression profile of Bcl-xL and Bax in platelets treated with ITP plasma. Normal washed platelets were treated with plasma from 20 active ITP patients or 10 age and gender-matched control to mimic the ITP in vivo environment. Mitochondrial depolarization, platelet apoptosis and activation were measured by flow cytometry. Expression of Bcl-xL, Bax and caspase-3 were also measured by quantitative real-time PCR and western blot. Our results demonstrated increased mitochondrial depolarization, platelet apoptosis and activation in platelets after treated with ITP plasma in comparison to control. In addition, decreased expression of Bcl-xL, increased expression of Bax and activity of caspase-3 were also observed. Furthermore, a negative correlation of Bcl-xL with Bax was found in platelets treated with ITP plasma. In conclusion, imbalanced expression of Bcl-xL and Bax might be associated with platelet apoptosis in ITP and therapeutically targeting them might be a novel approach in the treatment of ITP.