Sestrin2 protects against traumatic brain injury by reinforcing the activation of Nrf2 signaling

Sestrin2 (SESN2) is stress-inducible protein that confers cytoprotective effects against various noxious stimuli. Accumulating evidence has documented that SESN2 has potent anti-apoptosis and anti-oxidative stress functions. However, whether it provides neuroprotection in traumatic brain injury (TBI...

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Bibliographic Details
Published in:Human & experimental toxicology 2021-07, Vol.40 (7), p.1095-1111
Main Authors: Liu, Xiaobin, Li, Min, Zhu, Jiabao, Huang, Weidong, Song, Jinning
Format: Article
Language:English
Subjects:
Animal tissues
Antioxidants
Apoptosis
Brain
Cerebral cortex
Edema
Gene transfer
Head injuries
Neuroprotection
Oxidative stress
Pain perception
Signaling
Stress functions
Traumatic brain injury
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Summary:Sestrin2 (SESN2) is stress-inducible protein that confers cytoprotective effects against various noxious stimuli. Accumulating evidence has documented that SESN2 has potent anti-apoptosis and anti-oxidative stress functions. However, whether it provides neuroprotection in traumatic brain injury (TBI) models remains unexplored. The purpose of this study was to explore the regulatory effect of SESN2 on TBI using in vivo and in vitro models. We found that TBI resulted in a marked induction of SESN2 in the cerebral cortex tissues of mice. SESN2 overexpression in the brain by in vivo gene transfer significantly decreased neurological deficit, brain edema, and neuronal apoptosis of mice with TBI. Moreover, the overexpression of SESN2 significantly decreased the oxidative stress induced by TBI in mice. In vitro studies of TBI demonstrated that SESN2 overexpression decreased apoptosis and oxidative stress in scratch-injured cortical neurons. Notably, SESN2 overexpression increased the nuclear levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and enhanced the activation of Nrf2 antioxidant signaling in in vivo and in vitro models of TBI. In addition, the inhibition of Nrf2 significantly abolished SESN2-mediated neuroprotective effects in vivo and in vitro. In conclusion, these results of our work demonstrate that SESN2 protects against TBI by enhancing the activation of Nrf2 antioxidant signaling.
ISSN:0960-3271
1477-0903
DOI:10.1177/0960327120984224