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Tat-p27 Ameliorates Neuronal Damage Reducing α-Synuclein and Inflammatory Responses in Motor Neurons After Spinal Cord Ischemia

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Abstract

p27Kip1 (p27) regulates the cell cycle by inhibiting G1 progression in cells. Several studies have shown conflicting results on the effects of p27 against cell death in various insults. In the present study, we examined the neuroprotective effects of p27 against H2O2-induced oxidative stress in NSC34 cells and against spinal cord ischemia-induced neuronal damage in rabbits. To promote delivery into NSC34 cells and motor neurons in the spinal cord, Tat-p27 fusion protein and its control protein (Control-p27) were synthesized with or without Tat peptide, respectively. Tat-p27, but not Control-27, was efficiently introduced into NSC34 cells in a concentration- and time-dependent manner, and the protein was detected in the cytoplasm. Tat-p27 showed neuroprotective effects against oxidative stress induced by H2O2 treatment and reduced the formation of reactive oxygen species, DNA fragmentation, and lipid peroxidation in NSC34 cells. Tat-p27, but not Control-p27, ameliorated ischemia-induced neurological deficits and cell damage in the rabbit spinal cord. In addition, Tat-p27 treatment reduced the expression of α-synuclein, activation of microglia, and release of pro-inflammatory cytokines such as interleukin-1β and tumor necrosis factor-α in the spinal cord. Taken together, these results suggest that Tat-p27 inhibits neuronal damage by decreasing oxidative stress, α-synuclein expression, and inflammatory responses after ischemia.

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Data availability

The datasets and supporting materials generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2018R1A2B6001941 to Dae Won Kim) and by the Ministry of Education (2019R1A6A1A11036849 to Soo Young Choi).

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  1. Woosuk Kim and Hyun Jung Kwon are contributed equally to this article.

Authors and Affiliations

  1. Department of Biomedical Sciences, Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea

    Woosuk Kim, Hyun Jung Kwon & Soo Young Choi

  2. Department of Anatomy, College of Veterinary Medicine, and Veterinary Science Research Institute, Konkuk University, Seoul, 05030, South Korea

    Woosuk Kim

  3. Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, 25457, South Korea

    Hyun Jung Kwon & Dae Won Kim

  4. Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea

    Hyo Young Jung, Kyu Ri Hahn, Yeo Sung Yoon & In Koo Hwang

  5. Department of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 34134, South Korea

    Hyo Young Jung

  6. Department of Neurosurgery, Dongtan Sacred Heart Hospital, College of Medicine, Hallym University, Hwaseong, 18450, South Korea

    Seung Myung Moon

  7. Research Institute for Complementary & Alternative Medicine, Hallym University, Chuncheon, 24253, South Korea

    Seung Myung Moon

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Contributions

WK, HJK, HYJ, KRH, SMM, YSY, IKH, SYC, and DWK conceived the study. WK, HJK, SYC, and DWK designed the study and wrote the manuscript. WK, HYJ, and KRH conducted the animal experiments. HJK, DWK, and SYC conducted biochemical experiments. SMM, YSY, and IKH participated in designing and discussing the animal study. All authors have read and approved the final manuscript.

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Correspondence to Soo Young Choi or Dae Won Kim.

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Kim, W., Kwon, H.J., Jung, H.Y. et al. Tat-p27 Ameliorates Neuronal Damage Reducing α-Synuclein and Inflammatory Responses in Motor Neurons After Spinal Cord Ischemia. Neurochem Res 46, 3123–3134 (2021). https://doi.org/10.1007/s11064-021-03392-0

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