Autophagy plays an important role in triptolide-induced apoptosis in cardiomyocytes.

Abstract

Triptolide (TP), a major bioactive component isolated from the traditional Chinese herb Tripterygium wilfordii Hook f. (TWHF), has been shown to exert various pharmacological effects. However, the severe toxicity of TP prevents wide clinical use. In a previous study, we reported that TP-induced mitochondria-dependent apoptosis in cardiomyocytes is mediated by reactive oxygen species (ROS). Autophagy is a cellular self-digestion process and is one of the first lines of defense against oxidative stress. Additionally, recent evidence suggests that autophagy can selectively eliminate damaged mitochondria. This study investigated the role of autophagy in TP-induced cardiotoxicity. We investigated the effects of autophagy in combination with TP on apoptosis, ROS and mitochondrial function. Rat cardiomyocytes were pre-treated with chloroquine or rapamycin followed by TP. The augmentation of autophagy with rapamycin in the presence of TP substantially ameliorated the detrimental effects induced by TP, while suppression of autophagy by chloroquine accelerates TP-induced cellular damage. In addition, pre-treated with rapamycin before TP administration also attenuated TP-induced damage in Balb/c mice heart tissues. Taken together, these results suggest that TP-induced cell death can be modified by autophagy. Furthermore, induction of autophagy by rapamycin may be a potential cardioprotective role against TP-induced cardiotoxicity by facilitating removal of dysfunctional mitochondria.

DOI: 10.1016/j.toxlet.2015.05.013

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@article{Zhou2015AutophagyPA, title={Autophagy plays an important role in triptolide-induced apoptosis in cardiomyocytes.}, author={Jie H. S. Zhou and Chen Xi and Wenwen Wang and Yanqin Yang and Yuwen Qiu and Zhiying Huang}, journal={Toxicology letters}, year={2015}, volume={236 3}, pages={168-83} }