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Olaquindox-induced apoptosis is suppressed through p38 MAPK and ROS-mediated JNK pathways in HepG2 cells

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Abstract

We investigated mitogen-activated protein kinase (MAPK) pathways as well as reactive oxygen species (ROS) in olaquindox-induced apoptosis. Exposure of HepG2 cells to olaquindox resulted in the phosphorylation of p38 MAPK and c-Jun N-terminal kinases (JNK). To confirm the role of p38 MAPK and JNK, HepG2 cells were pretreated with MAPKs-specific inhibitors prior to olaquindox treatment. Olaquindox-induced apoptosis was significantly potentiated by the JNK inhibitor (SP600125) or the p38 MAPK inhibitor (SB203580). Furthermore, we observed that olaquindox treatment led to ROS generation and that olaquindox-induced apoptosis and ROS generation were both significantly reduced by the antioxidants, superoxide dismutase and catalase. In addition, the levels of phosphorylation of JNK, but not p38 MAPK, were significantly suppressed after pretreatment of the antioxidants, while inhibition of the activations of JNK or p38 MAPK had no effect on ROS generation. This result suggested that ROS may be the upstream mediator for the activation of JNK. Conclusively, our results suggested that apoptosis in response to olaquindox treatment in HepG2 cells might be suppressed through p38 MAPK and ROS–JNK pathways.

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Abbreviations

HepG2 cells:

Human hepatoma G2 cells

ROS:

Reactive oxygen species

MAPKs:

Mitogen-activated protein kinases

ERK1/2:

Extracellular signal-regulated kinases 1/2

JNK:

c-Jun N-terminal kinases

SOD:

Superoxide dismutase

DMSO:

Dimethyl sulfoxide

PI:

Propidium iodide

DCF-DA:

2,7-Dichlorodihydrofluorescein diacetate

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Acknowledgments

This work was supported by the Basic Exclusive Research Fund for Central Universities from the Ministry of Education of the People’s Republic of China (2011JS009).

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People’s Republic of China

    Wen-xia Zhao, Shu-sheng Tang, Xi Jin, Chao-ming Zhang, Ting Zhang, Cong-cong Wang, Yu Sun & Xi-long Xiao

  2. The Center for Drug Safety Evaluation, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China

    Wen-xia Zhao

  3. College of Life Sciences, Beijing Normal University, Beijing, 100875, People’s Republic of China

    Xi Jin

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  1. Wen-xia Zhao
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  2. Shu-sheng Tang
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Correspondence to Xi-long Xiao.

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Zhao, Wx., Tang, Ss., Jin, X. et al. Olaquindox-induced apoptosis is suppressed through p38 MAPK and ROS-mediated JNK pathways in HepG2 cells. Cell Biol Toxicol 29, 229–238 (2013). https://doi.org/10.1007/s10565-013-9249-y

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  • DOI: https://doi.org/10.1007/s10565-013-9249-y

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