Exogenous Alpha-Ketoglutaric Acid Alleviates the Rabbit Dermal Papilla Cell Oxidative Damage Caused by Hydrogen
Xiaosong Wang1, Shu Li1, Jiali Chen1
1Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Nutrition and Efficient Feeding, Department of Animal Science and Technology, Shandong Agricultural University, Tai'an 271017, China.
Abstract:
As an endogenous metabolite, α-ketoglutarate (AKG) exhibits potent antioxidant properties, yet its molecular mechanisms remain unclear. Dermal Papilla Cells (DPCs), functioning as the regulatory hub of hair follicle morphogenesis, serve as a pivotal model system for deciphering follicular functionality and regeneration mechanisms through their orchestration of signaling networks. Using a hydrogen peroxide (H2O2)-induced oxidative stress model in DPCs, we investigated AKG's protective effects. AKG attenuated H2O2-triggered reactive oxygen species (ROS) overproduction, restored mitochondrial membrane potential, and suppressed apoptosis-related protein dysregulation. It enhanced cellular stress resistance by increasing the Bcl-2/Bax ratio, boosting antioxidant levels, and inhibiting inflammation. Mechanistically, H2O2 activated the Nrf2 pathway, while AKG amplified Nrf2 nuclear translocation and expression. Crucially, ERK inhibition abrogated AKG-mediated Nrf2 regulation, intensifying ROS accumulation and cell death. These results identify the ERK/Nrf2 axis as central to AKG's antioxidative cytoprotection. This study advances AKG's therapeutic potential and deepens insights into its multifunctional roles.
