Selenium ameliorates cadmium-induced mouse leydig TM3 cell apoptosis via inhibiting the ROS/JNK /c-jun signaling
Xiangmei Ren1, Susu Wang1, Chaoqin Zhang1
1Department of Nutrition, School of Public Health, Xuzhou Medical University, China.
Abstract:
Despite the well-known acknowledgement of both the toxicity of cadmium (Cd) and the ameliorative effect of selenium (Se), the mechanism of the protective effect of selenium on cadmium-induced Mouse Leydig (TM3) cell apoptosis remains unknown. In this study, we hypothesized that the reactive oxygen species (ROS)-mediated c-jun N-terminal kinase (JNK) signaling pathway is involved in anti-apoptosis of selenium against cadmium in TM3 cells. We found that exposure to cadmium caused evident cytotoxicity, in which cell viability was inhibited, followed by inducement of apoptosis. Moreover, the level of ROS generation was elevated, leading to the phosphorylation of JNK. In addition, following cadmium exposure, the nuclear transcription factor c-jun was significantly activated, which led to increased expression of downstream gene c-jun, resulting in downstream activation of the apoptosis-related protein Caspase3 and upregulation of Cleaved-PARP, as well as inhibition of the anti-apoptosis protein Bcl-2. However, pretreatment with selenium remarkably suppressed cadmium-induced TM3 cell apoptosis. Furthermore, the level of ROS declined, and the JNK signaling pathway was blocked. Following this, the gene expression of c-jun decreased while Bcl-2 increased, which was consistent with the effects on proteins, that Caspase3 activity and Cleaved-PARP were inhibited while Bcl-2 level was restored. In order to explain the relationship between molecules of the signaling pathway, N-acetyl-L-cysteine (NAC), the ROS inhibitor, and JNK1/2 siRNA were administered, which further indicated the mediatory role of the ROS/JNK/c-jun signaling pathway in regulating anti-apoptosis of selenium against cadmium-induced TM3 cell apoptosis.
Insights
Selenium protects mouse Leydig cells from cadmium toxicity by inhibiting the reactive oxygen species (ROS)/JNK/c-jun pathway, thereby preventing apoptosis. This mechanism highlights selenium
Area of Science:
- Toxicology
- Cell Biology
- Biochemistry
Background:
- Cadmium (Cd) is a toxic heavy metal with known adverse effects on cell viability.
- Selenium (Se) is recognized for its protective properties against heavy metal toxicity.
- The precise mechanism of selenium's protection against cadmium-induced apoptosis in Mouse Leydig (TM3) cells is not fully understood.
Purpose of the Study:
- To investigate the role of the reactive oxygen species (ROS)-mediated c-jun N-terminal kinase (JNK) signaling pathway in selenium's protective effect against cadmium-induced apoptosis in TM3 cells.
Main Methods:
- TM3 cells were exposed to cadmium, with or without selenium pretreatment.
- Reactive oxygen species (ROS) generation, JNK signaling pathway activation, and apoptosis-related proteins (Caspase3, Cleaved-PARP, Bcl-2) were assessed.
- N-acetyl-L-cysteine (NAC) and JNK1/2 siRNA were used to confirm the involvement of the ROS/JNK/c-jun pathway.
Main Results:
- Cadmium exposure induced TM3 cell apoptosis, increased ROS levels, and activated the JNK/c-jun pathway, leading to altered expression of apoptosis-related proteins.
- Selenium pretreatment significantly reduced cadmium-induced apoptosis, decreased ROS, and inhibited the JNK/c-jun pathway.
- Selenium restored Bcl-2 levels and suppressed Caspase3 activity and Cleaved-PARP, confirming its anti-apoptotic role.
Conclusions:
- The ROS/JNK/c-jun signaling pathway is a key mediator of selenium's protective effect against cadmium-induced apoptosis in TM3 cells.
- Selenium mitigates cadmium toxicity by blocking ROS generation and downstream JNK/c-jun activation.
- Understanding this mechanism provides insights into preventing cadmium-induced testicular damage.