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Tat-p27 Ameliorates Neuronal Damage Reducing α-Synuclein and Inflammatory Responses in Motor Neurons After Spinal Cord Ischemia.
- Source :
-
Neurochemical research [Neurochem Res] 2021 Dec; Vol. 46 (12), pp. 3123-3134. Date of Electronic Publication: 2021 Aug 17. - Publication Year :
- 2021
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Abstract
- p27 <superscript>Kip1</superscript>  (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 H <subscript>2</subscript> O <subscript>2</subscript> -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 H <subscript>2</subscript> O <subscript>2</subscript> 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.<br /> (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1573-6903
- Volume :
- 46
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Neurochemical research
- Publication Type :
- Academic Journal
- Accession number :
- 34403064
- Full Text :
- https://doi.org/10.1007/s11064-021-03392-0