Institute of Neurobiology, Binzhou Medical University, 346 Guanhai Road, Laishan, 264003, Shandong, China.
Department of Anatomy, School of Basic Medicine, Shandong University, Jinan, Shandong, 250021, China; School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, 266071, China.
Neurochem Int. 2024 Nov;180:105885. doi: 10.1016/j.neuint.2024.105885. Epub 2024 Oct 19.
In the secondary injury stage of spinal cord injury, mitochondrial dysfunction leads to decreased ATP production, increased ROS production, and activation of the mitochondria-mediated apoptosis signaling pathway. This ultimately intensifies neuronal death and promotes the progression of the injury. Apelin, a peptide produced by the APLN gene, has demonstrated promise in the treatment of spinal cord injury. The aim of this study was to investigate how Apelin protects neurons after spinal cord injury by influencing the mitochondrial dynamics. The results showed that Apelin has the ability to reduce mitochondrial fission, enhance the mitochondrial membrane potential, improve antioxidant capacity, facilitate the clearance of excess ROS, and ultimately decrease apoptosis in PC12 cells. Moreover, Apelin is overexpressed in neurons in the damaged part of the spinal cord, contributing to reduce mitochondrial fission, improve antioxidant capacity, increase ATP production, decrease apoptosis, promote spinal cord morphological repair, maintain the number of nissl bodies, and enhance signal transduction in the descending spinal cord pathway. Apelin exerts its protective effect by inhibiting the Mst1-JNK-Drp1 signaling pathway. In summary, our study further improved the effect of Apelin in the treatment of spinal cord injury, revealed the mechanism of Apelin in protecting damaged neurons after spinal cord injury by maintaining mitochondrial homeostasis, and provided a new therapeutic mechanism for Apelin in spinal cord injury.
在脊髓损伤的继发性损伤阶段，线粒体功能障碍导致 ATP 生成减少、ROS 生成增加和线粒体介导的细胞凋亡信号通路激活。这最终加剧了神经元死亡，并促进了损伤的进展。Apelin 是一种由 APLN 基因产生的肽，在脊髓损伤的治疗中显示出了潜力。本研究旨在探讨 Apelin 通过影响线粒体动力学如何保护脊髓损伤后的神经元。结果表明，Apelin 具有减少线粒体分裂、增强线粒体膜电位、提高抗氧化能力、促进多余 ROS 清除以及最终减少 PC12 细胞凋亡的能力。此外，Apelin 在脊髓损伤部位的神经元中过度表达，有助于减少线粒体分裂、提高抗氧化能力、增加 ATP 生成、减少凋亡、促进脊髓形态修复、维持尼氏体数量，并增强下行脊髓通路中的信号转导。Apelin 通过抑制 Mst1-JNK-Drp1 信号通路发挥其保护作用。总之，我们的研究进一步提高了 Apelin 在治疗脊髓损伤中的效果，揭示了 Apelin 通过维持线粒体稳态来保护脊髓损伤后受损神经元的机制，并为 Apelin 在脊髓损伤中的治疗提供了新的机制。
