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Open AccessArticle

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

by Zhicheng Wang 1,*,†, Jie Wang 1,†, Rufeng Xie 2, Ruilai Liu 1 and Yuan Lu 1,*
1
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
2
Blood Engineering Laboratory, Shanghai Blood Center, Shanghai 200051, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Lars Olson, Jaime M. Ross and Giuseppe Coppotelli
Int. J. Mol. Sci. 2015, 16(5), 11087-11100; https://doi.org/10.3390/ijms160511087
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)
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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