Next Article in Journal
Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells
Next Article in Special Issue
Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction
Previous Article in Journal
Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment
Previous Article in Special Issue
Borrowing Nuclear DNA Helicases to Protect Mitochondrial DNA
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2015, 16(5), 11087-11100; doi:10.3390/ijms160511087

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

1,†,* , 1,†
,
2
,
1
and
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
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)
View Full-Text   |   Download PDF [964 KB, uploaded 15 May 2015]   |  

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. View Full-Text
Keywords: platelets; mitochondria; reactive oxygen species; doxorubicin; apoptosis platelets; mitochondria; reactive oxygen species; doxorubicin; apoptosis
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top