• World Neurosurg · Aug 2023

    N-acetylserotonin protects rat nucleus pulposus cells against oxidative stress injury by activating the PI3K/AKT signaling pathway.

    • Wang Yidian, Kang Jihe, Guo Xudong, Zhu Daxue, Liu Mingqiang, and Kang Xuewen.
    • The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, PR China; Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
    • World Neurosurg. 2023 Aug 1; 176: e109e124e109-e124.

    BackgroundCurrent studies suggest that the pathogenesis of intervertebral disc degeneration (IDD) is related to oxidative stress damage in nucleus pulposus cells (NPCs). N-acetylserotonin (NAS) is an effective scavenger of reactive oxygen species, but its role in IDD and its underlying mechanisms are not yet clear. Therefore, the aim of this study was to investigate the effect of NAS on oxidative stress injury in NPCs and its mechanism.MethodsNP tissue of rat intervertebral disc was collected and NPCs were isolated. NPCs were treated with H2O2 to simulate the state of oxidative stress. The effects of NAS on cell viability, apoptosis, senescence, extracellular matrix (ECM), redox status and PI3K/AKT signal pathway were evaluated by cell counting kit-8, western blot, immunofluorescence, flow cytometry and SA-β-gal staining. Finally, the changes of the above indexes were further observed after the inhibition of PI3K pathway by LY294002.ResultsFlow cytometry showed that NAS reduced H2O2-induced apoptosis of NPCs. SA-β-Gal staining showed that H2O2-induced senescence of NP cells was reversed by NAS. Immunofluorescence staining showed that NAS inhibited H2O2-induced ECM degradation. Western blotting analysis revealed that NAS significantly decreased apoptosis, senescence and ECM degradation. Further analysis showed that NAS treatment activated the PI3K/AKT pathway in H2O2-stimulated NPCs. However, these protected effects were inhibited after LY294002 treatment.ConclusionsThe results of the present study suggest that NAS inhibits H2O2-induced NPCs degeneration by activating PI3K/AKT pathway, suggesting that NAS has the potential to treat IDD.Copyright © 2023. Published by Elsevier Inc.

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