Abstract
It has been reported that ophiopogonin D (OP-D), a steroidal glycoside and an active component extracted from Ophiopogon japonicas, promotes antioxidative protection of the cardiovascular system. However, it is unknown whether OP-D exerts protective effects against doxorubicin (DOX)-induced autophagic cardiomyocyte injury. Here, we demonstrate that DOX induced excessive autophagy through the generation of reactive oxygen species (ROS) in H9c2 cells and in mouse hearts, which was indicated by a significant increase in the number of autophagic vacuoles, LC3-II/LC3-I ratio, and upregulation of the expression of GFP-LC3. Pretreatment with OP-D partially attenuated the above phenomena, similar to the effects of treatment with 3-methyladenine. In addition, OP-D treatment significantly relieved the disruption of the mitochondrial membrane potential by antioxidative effects through downregulating the expression of both phosphorylated c-Jun N-terminal kinase and extracellular signal-regulated kinase. The ability of OP-D to reduce the generation of ROS due to mitochondrial damage and, consequently, to inhibit autophagic activity partially accounts for its protective effects in the hearts against DOX-induced toxicity.
Footnotes
- Received August 11, 2014.
- Accepted November 4, 2014.
Y.-Y.Z. and C.M. contributed equally to this work.
This work was supported by the National Natural Science Foundation of China [Grants 30871228, 31171302]; the Opening Project of Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology at Nanjing Normal University [Grant 2011MMBKF04]; and the project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions [Grant 164320H106]. Z.Z. and C.L. are the associate fellows at the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine of Nanjing Medical University.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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