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Int. J. Mol. Sci. 2015, 16(5), 11087-11100;

Mitochondria-Derived Reactive Oxygen Species Play an Important Role in Doxorubicin-Induced Platelet Apoptosis

1,†,* , 1,†
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
Blood Engineering Laboratory, Shanghai Blood Center, Shanghai 200051, China
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editors: Lars Olson, Jaime M. Ross and Giuseppe Coppotelli
Received: 30 March 2015 / Revised: 4 May 2015 / Accepted: 11 May 2015 / Published: 15 May 2015
(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)
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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. View Full-Text
Keywords: platelets; mitochondria; reactive oxygen species; doxorubicin; apoptosis platelets; mitochondria; reactive oxygen species; doxorubicin; apoptosis

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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.

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