Mitochondria-Derived Reactive Oxygen Species Play an Important Role in Doxorubicin-Induced Platelet Apoptosis
AbstractDoxorubicin (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. View Full-Text
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Wang, Z.; Wang, J.; Xie, R.; Liu, R.; Lu, Y. Mitochondria-Derived Reactive Oxygen Species Play an Important Role in Doxorubicin-Induced Platelet Apoptosis. Int. J. Mol. Sci. 2015, 16, 11087-11100.
Wang Z, Wang J, Xie R, Liu R, Lu Y. Mitochondria-Derived Reactive Oxygen Species Play an Important Role in Doxorubicin-Induced Platelet Apoptosis. International Journal of Molecular Sciences. 2015; 16(5):11087-11100.Chicago/Turabian Style
Wang, Zhicheng; Wang, Jie; Xie, Rufeng; Liu, Ruilai; Lu, Yuan. 2015. "Mitochondria-Derived Reactive Oxygen Species Play an Important Role in Doxorubicin-Induced Platelet Apoptosis." Int. J. Mol. Sci. 16, no. 5: 11087-11100.