Mitochondria-derived reactive oxygen species play an important role in Doxorubicin-induced platelet apoptosis.
Mitochondria-derived reactive oxygen species play an important role in Doxorubicin-induced platelet apoptosis.
复制标题
线粒体衍生的活性氧在阿霉素诱导的血小板凋亡中发挥重要作用。
DOI：
10.3390/ijms160511087
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发表时间：
2015-05-15
影响因子：
5.6
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Wang Z;Wang J;Xie R;Liu R;Lu Y
阿霉素(DOX)是一种有效的化疗药物，但其使用受到一些副作用的限制，如心脏毒性和血小板减少。DOX所致的心脏毒性已被广泛研究，然而，DOX所致的血小板减少症尚不清楚。在这里，我们发现阿霉素诱导的线粒体介导的内源性细胞凋亡和糖蛋白(GP)Ibα在血小板中脱落。DOX不能诱导血小板活化；而DOX能明显降低二磷酸腺苷(ADP)和凝血酶诱导的血小板聚集，并削弱血小板与von Willebrand因子(VWF)表面的黏附。此外，我们还发现DOX以剂量依赖的方式诱导细胞内ROS的产生和线粒体ROS的产生。针对线粒体的ROS清除剂Mito-Tempo阻止了细胞内ROS和线粒体ROS的产生。此外，Mito-Tempo还可减少阿霉素诱导的血小板凋亡和GPIBα的脱落。这些数据表明DOX诱导了血小板的凋亡，损害了血小板的功能。线粒体ROS在阿霉素诱导的血小板凋亡和GPIBα脱落中起关键作用。因此，DOX诱导的血小板凋亡可能参与了DOX引发的血小板减少症；线粒体靶向ROS清除剂在涉及线粒体氧化损伤的血小板相关疾病中具有潜在的临床应用价值。
Doxorubicin (DOX) is an effective chemotherapeutic agent; however; its use is limited by some side effects; such as cardiotoxicity and thrombocytopenia. DOX-induced cardiotoxicity has been intensively investigated; however; DOX-induced thrombocytopenia has not been clearly elucidated. Here we show that DOX-induced mitochondria-mediated intrinsic apoptosis and glycoprotein (GP)Ibα shedding in platelets. DOX did not induce platelet activation; whereas; DOX obviously reduced adenosine diphosphate (ADP)- and thrombin-induced platelet aggregation; and impaired platelet adhesion on the von Willebrand factor (vWF) surface. In addition; we also show that DOX induced intracellular reactive oxygen species (ROS) production and mitochondrial ROS generation in a dose-dependent manner. The mitochondria-targeted ROS scavenger Mito-TEMPO blocked intracellular ROS and mitochondrial ROS generation. Furthermore; Mito-TEMPO reduced DOX-induced platelet apoptosis and GPIbα shedding. These data indicate that DOX induces platelet apoptosis; and impairs platelet function. Mitochondrial ROS play a pivotal role in DOX-induced platelet apoptosis and GPIbα shedding. Therefore; DOX-induced platelet apoptosis might contribute to DOX-triggered thrombocytopenia; and mitochondria-targeted ROS scavenger would have potential clinical utility in platelet-associated disorders involving mitochondrial oxidative damage.
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影响因子：
10.4
作者：
Kim, E. -J.;Lim, K. -M.;Chung, J. -H.
通讯作者：
Chung, J. -H.
影响因子：
4.1
作者：
Koziel, Rafal;Pircher, Haymo;Jansen-Duerr, Pidder
通讯作者：
Jansen-Duerr, Pidder
影响因子：
3.9
作者：
Wang, Zhicheng;Shi, Quanwei;Dai, Kesheng
通讯作者：
Dai, Kesheng
影响因子：
4.3
作者：
Li, T;Danelisen, I;Singal, PK
通讯作者：
Singal, PK
影响因子：
--
作者：
Shokoohinia Y;Hosseinzadeh L;Moieni-Arya M;Mostafaie A;Mohammadi-Motlagh HR
通讯作者：
Mohammadi-Motlagh HR