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Olaquindox-induced apoptosis is suppressed through p38 MAPK and ROS-mediated JNK pathways in HepG2 cells
Wen-Xia Zhao1, Shu-Sheng Tang, Xi Jin
1Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People's Republic of China.
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.
Insights
Olaquindox triggers apoptosis in HepG2 cells via p38 MAPK and ROS-JNK pathways. Antioxidants reduce this effect, suggesting a protective role against olaquindox toxicity.
Area of Science:
- Cell Biology
- Biochemistry
- Toxicology
Background:
- Mitogen-activated protein kinase (MAPK) pathways are crucial in cellular signaling.
- Reactive oxygen species (ROS) play a role in various cellular processes, including apoptosis.
- Olaquindox is an antimicrobial agent whose cellular effects require further elucidation.
Purpose of the Study:
- To investigate the role of MAPK pathways and ROS in olaquindox-induced apoptosis in HepG2 cells.
- To elucidate the relationship between ROS generation and MAPK activation in response to olaquindox.
Main Methods:
- HepG2 cells were treated with olaquindox.
- Specific inhibitors for p38 MAPK (SB203580) and JNK (SP600125) were used.
- Antioxidants (superoxide dismutase and catalase) were employed to assess ROS involvement.
- Western blotting was used to detect phosphorylation of p38 MAPK and JNK.
Main Results:
- Olaquindox induced apoptosis, p38 MAPK, and JNK phosphorylation in HepG2 cells.
- Inhibiting JNK or p38 MAPK potentiated olaquindox-induced apoptosis.
- Olaquindox treatment led to ROS generation, which was reduced by antioxidants.
- Antioxidants suppressed JNK phosphorylation, but not p38 MAPK, suggesting ROS acts upstream of JNK.
Conclusions:
- Apoptosis induced by olaquindox in HepG2 cells involves both p38 MAPK and ROS-JNK signaling pathways.
- ROS generation appears to be an upstream mediator for JNK activation in this context.
- Targeting these pathways may offer a strategy to mitigate olaquindox-induced cellular damage.
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