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Senegenin Rescues PC12 Cells with Oxidative Damage Through Inhibition of Ferroptosis

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Abstract

Oxidative stress is one of the pathological mechanisms of Alzheimer’s disease (AD), and ferroptosis has been determined to be involved in neurodegenerative diseases such as AD. Senegenin (Sen) prevents oxidative damage in nerve cells via a mechanism that may be highly related to ferroptosis. However, the mechanism of ferroptosis pathway involvement in AD is unclear. In this study, we established a model of PC12 cytotoxic injury induced by Aβ25–35, and we detected the level of oxidative damage, MMP, and ferroptosis-related protein expression. The results showed that, compared with control group, the level of ROS increased, GPX activities decreased, and MDA levels increased in Aβ25–35 group. Aβ25–35 could induce mitochondrial depolarization in PC12 cells and Fer-1 could not reverse this damage. WB revealed that Aβ25–35 group had increased ACSL4 and PEBP1 proteins, and decreased GPX4 protein. After adding Sen in the model, the level of oxidative damage was reduced, and mitochondrial depolarization was reversed compared with Aβ25–35 group. WB suggested that the expression of ACSL4 and PEBP1 proteins decreased, and the expression of GPX4 protein increased by Sen treatment. In conclusion, we found that Sen exhibits strong neuroprotective activity against Aβ25–35 induced oxidative damage and lipid metabolic associated with ferroptosis. Inhibiting nerve cell ferroptosis might facilitate the future development of strategies to AD.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank all the participants of the present study as well as all the members of staff of the Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine.

Funding

This work was supported by the Natural Science Foundation of Guangdong province (No. 2014A030313394), the Project of Science and Technology of Guangzhou (2014J4100098), the Fundamental Research Funds for the Central Universities in China (No. 21613401), and the Project of Science and Technology Plan in Guangzhou: City-University (Hospital) joint funding (202201020016).

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  1. Heping Zhang, Wei Zhou, Jianling Li and Zhaohui Qiu contributed equally to this work.

Authors and Affiliations

  1. Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine, School of Medicine, Jinan University, No. 601 Avenue Huangpu West, Guangzhou, 510632, Guangdong, China

    Heping Zhang, Zhaohui Qiu, Xiaotong Wang, Hui Xu, Huadong Wang, Daxiang Lu & Renbin Qi

  2. Department of Internal Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, China

    Wei Zhou

  3. Department of Pathology, Guangzhou Chest Hospital, No. 62 Hengzhigang Rd, Guangzhou, 510095, Guangdong, China

    Wei Zhou

  4. Department of Anesthesiology, First Affiliated Hospital of Jinan University, Guangdong, 510630, Guangzhou, China

    Jianling Li

  5. Department of Pathology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, Guangdong, China

    Zhaohui Qiu

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  1. Heping Zhang
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Contributions

All the authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Heping Zhang, Wei Zhou, Jianling Li, and Zhaohui Qiu. The first draft of the manuscript was written by Heping Zhang, and all the authors commented on the previous versions of the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Renbin Qi.

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Zhang, H., Zhou, W., Li, J. et al. Senegenin Rescues PC12 Cells with Oxidative Damage Through Inhibition of Ferroptosis. Mol Neurobiol 59, 6983–6992 (2022). https://doi.org/10.1007/s12035-022-03014-y

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