1. Tat-p27 Ameliorates Neuronal Damage Reducing α-Synuclein and Inflammatory Responses in Motor Neurons After Spinal Cord Ischemia.
- Author
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Kim W, Kwon HJ, Jung HY, Hahn KR, Moon SM, Yoon YS, Hwang IK, Choi SY, and Kim DW
- Subjects
- Animals, Inflammation drug therapy, Inflammation metabolism, Lipid Peroxidation, Male, Motor Neuron Disease etiology, Motor Neuron Disease metabolism, Motor Neuron Disease pathology, Neurons metabolism, Neurons pathology, Oxidative Stress, Rabbits, Reactive Oxygen Species metabolism, Gene Products, tat administration & dosage, Inflammation immunology, Motor Neuron Disease prevention & control, Neurons drug effects, Neuroprotective Agents pharmacology, Spinal Cord Ischemia complications, alpha-Synuclein antagonists & inhibitors
- Abstract
p27
Kip1 (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 H2 O2 -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 H2 O2 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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2021
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