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PTD-FNK Alleviated LPS-Induced Oxidative Stress of Boar Testicular Sertoli Cells via Keap1-Nrf2 Pathway
Weixia Ji1, Qiuyan Huang1,2, Qiqi Ma1
1College of Animal Science and Technology, Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, Guangxi University, Nanning 530004, China.
Abstract:
PTD-FNK, a synthetic anti-apoptotic protein, has been shown to potently alleviate cellular injuries. However, the effects of PTD-FNK on oxidative defense in boar testicular Sertoli cells (SCs) against oxidative injury has not been explored. In this study, we show that exposure of SCs to 100 mg/L lipopolysaccharide (LPS) for 12 h leads to decreased survival rate, superoxide dismutase (SOD) activity, and increased malondialdehyde (MDA). Treatment with 0.01 nmol/L PTD-FNK for 4 h significantly enhanced the activity of SOD, catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in SCs. Concurrently, PTD-FNK treatment effectively reduced the production of reactive oxygen species (ROS) and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in SCs. Moreover, using His pull-down and LC-MS techniques, we identified PTD-FNK-interacting proteins and confirmed that this protective effect may be mediated by the regulation of the Keap1-Nrf2 signaling pathway by PTD-FNK. Therefore, PTD-FNK alleviates LPS-induced oxidative stress via the Keap1/Nrf2 pathway, providing novel insights for the development of therapeutic agents targeting testicular oxidative damage.
Insights
PTD-FNK protects boar Sertoli cells from oxidative damage by boosting antioxidant enzymes and reducing harmful byproducts. This protein may offer a new therapeutic approach for testicular oxidative stress.
Area of Science:
- Reproductive Biology
- Cellular Biology
- Oxidative Stress Research
Background:
- Boar Sertoli cells (SCs) are crucial for testicular function.
- Oxidative stress negatively impacts SCs and male fertility.
- The protective effects of PTD-FNK on SCs against oxidative injury remain uninvestigated.
Purpose of the Study:
- To investigate the protective effects of PTD-FNK against lipopolysaccharide (LPS)-induced oxidative stress in boar SCs.
- To elucidate the underlying mechanisms, including the Keap1-Nrf2 signaling pathway.
Main Methods:
- Boar SCs were exposed to LPS to induce oxidative stress.
- Cells were treated with PTD-FNK.
- Assays were performed to measure cell viability, antioxidant enzyme activities (SOD, CAT, GSH-Px), total antioxidant capacity (T-AOC), reactive oxygen species (ROS), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels.
- His pull-down and LC-MS were used to identify PTD-FNK-interacting proteins.
Main Results:
- LPS exposure decreased SC survival and antioxidant capacity while increasing oxidative damage markers (MDA, ROS, 8-OHdG).
- PTD-FNK treatment significantly enhanced SOD, CAT, GSH-Px, and T-AOC activities.
- PTD-FNK treatment reduced ROS and 8-OHdG levels.
- PTD-FNK was found to interact with proteins involved in the Keap1-Nrf2 pathway.
Conclusions:
- PTD-FNK effectively alleviates LPS-induced oxidative stress in boar testicular Sertoli cells.
- The protective mechanism involves the enhancement of antioxidant defense and the regulation of the Keap1/Nrf2 signaling pathway.
- PTD-FNK shows potential as a therapeutic agent for testicular oxidative damage.
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