Inhibition of TRPA1 Attenuates Oxidative Stress-induced Damage After Traumatic Brain Injury via the ERK/AKT Signaling Pathway.

Autor: Yang XJ; The Translational Research Institute for Neurological Disorders, Department of Neurosurgery, The First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu, China., Ling S; The Translational Research Institute for Neurological Disorders, Department of Neurosurgery, The First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu, China., Zhou ML; Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Jiangsu, China., Deng HJ; Department of Neurosurgery, The First Affiliated Hospital, Guangxi Medical University, Nanning, China., Qi M; The Translational Research Institute for Neurological Disorders, Department of Neurosurgery, The First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu, China., Liu XL; The Translational Research Institute for Neurological Disorders, Department of Neurosurgery, The First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu, China., Zhen C; Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu, China., Chen YX; The Translational Research Institute for Neurological Disorders, Department of Neurosurgery, The First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu, China., Fan XR; The Translational Research Institute for Neurological Disorders, Department of Neurosurgery, The First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu, China., Wu ZY; The Translational Research Institute for Neurological Disorders, Department of Neurosurgery, The First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu, China., Ma FC; The Translational Research Institute for Neurological Disorders, Department of Neurosurgery, The First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu, China., Rong J; The Translational Research Institute for Neurological Disorders, Department of Neurosurgery, The First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu, China., Di GF; The Translational Research Institute for Neurological Disorders, Department of Neurosurgery, The First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu, China. Electronic address: wuhusjwk@163.com., Jiang XC; The Translational Research Institute for Neurological Disorders, Department of Neurosurgery, The First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu, China. Electronic address: jiangxiaochun2019@hotmail.com.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2022 Jul 01; Vol. 494, pp. 51-68. Date of Electronic Publication: 2022 Feb 11.
DOI: 10.1016/j.neuroscience.2022.02.003
Abstrakt: Neuron apoptosis is a feature of secondary injury after traumatic brain injury (TBI). Evidence implies that excess calcium (Ca 2+ ) ions and reactive oxidative species (ROS) play critical roles in apoptosis. In reaction to increased ROS, the anti-oxidative master transcription factor, Transient receptor potential Ankyrin 1 (TRPA1) allows Ca 2+ ions to enter cells. However, the effect of TBI on the expression of TRPA1 and the role of TRPA1 in TBI are unclear. In the present study, TBI in the mouse brain was simulated using the weight-drop model. The process of neuronal oxidative stress was simulated in HT22 neuronal cells by treatment with hydrogen peroxide. We found that TRPA1 was significantly upregulated in neurons at 24 h after TBI. Neuronal apoptosis was increased in the in vivo and in vitro models; however, this increase was reduced by the functional inhibition of TRPA1 in both models. After TBI, TRPA1 was upregulated via nuclear factor, erythroid 2 like 2 (Nrf2) in neurons. TRPA1-mediated neuronal apoptosis after TBI might be achieved in part through the CaMKII/AKT/ERK signaling pathway. To sum up, TBI-triggered TRPA1 upregulation in neurons is mediated by Nrf2 and the functional blockade of TRPA1 attenuates neuronal apoptosis and improves neuronal dysfunction, partially mediated through the activation of the calcium/calmodulin dependent protein kinase II (CaMKII) extracellular regulated kinase (ERK)/protein kinase B (AKT) signaling pathway. Our results suggest that functional blockade of TRPA1 might be a promising therapeutic intervention related to ROS and Nrf2 in TBI.
(Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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