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Mitochondria-derived reactive oxygen species play an important role in Doxorubicin-induced platelet apoptosis.
Wang, Zhicheng; Wang, Jie; Xie, Rufeng; Liu, Ruilai; Lu, Yuan.
Afiliación
  • Wang Z; Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China. ahwzc@126.com.
  • Wang J; Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China. Jiewang2015@126.com.
  • Xie R; Blood Engineering Laboratory, Shanghai Blood Center, Shanghai 200051, China. xierufeng555@163.com.
  • Liu R; Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China. liuruilai88@163.com.
  • Lu Y; Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China. yuanlu@hsh.stn.sh.cn.
Int J Mol Sci ; 16(5): 11087-100, 2015 May 15.
Article en En | MEDLINE | ID: mdl-25988386
ABSTRACT
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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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Doxorrubicina / Especies Reactivas de Oxígeno / Apoptosis / Mitocondrias Límite: Adult / Female / Humans / Male Idioma: En Revista: Int J Mol Sci Año: 2015 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Doxorrubicina / Especies Reactivas de Oxígeno / Apoptosis / Mitocondrias Límite: Adult / Female / Humans / Male Idioma: En Revista: Int J Mol Sci Año: 2015 Tipo del documento: Article País de afiliación: China