MEK1/2 Inhibition Synergistically Enhances the Preventive Effects of Normobaric Oxygen on Spinal Cord Injury in Decompression Sickness Rats

A previous study from our team found that hyperbaric oxygen (HBO) pretreatment attenuated decompression sickness (DCS) spinal cord injury by upregulating heat shock protein 32 (HSP32) via the ROS/p38 MAPK pathway. Meanwhile, a MEK1/2-negative regulatory pathway was also activated to inhibit HSP32 ov...

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Main Authors: Quan Zhou, Xiangyang Meng, Guoyang Huang, Hongjie Yi, Juan Zheng, Kun Zhang, Weigang Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-06-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2021.674430/full
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author Quan Zhou
Xiangyang Meng
Guoyang Huang
Hongjie Yi
Juan Zheng
Kun Zhang
Weigang Xu
author_facet Quan Zhou
Xiangyang Meng
Guoyang Huang
Hongjie Yi
Juan Zheng
Kun Zhang
Weigang Xu
author_sort Quan Zhou
collection DOAJ
description A previous study from our team found that hyperbaric oxygen (HBO) pretreatment attenuated decompression sickness (DCS) spinal cord injury by upregulating heat shock protein 32 (HSP32) via the ROS/p38 MAPK pathway. Meanwhile, a MEK1/2-negative regulatory pathway was also activated to inhibit HSP32 overexpression. The purpose of this study was to determine if normobaric oxygen (NBO) might effectively induce HSP32 while concurrently inhibiting MEK1/2 and to observe any protective effects on spinal cord injury in DCS rats. The expression of HSP32 in spinal cord tissue was measured at 6, 12, 18, and 24 h following NBO and MEK1/2 inhibitor U0126 pretreatment. The peak time of HSP32 was observed at 12 h after simulated air diving. Subsequently, signs of DCS, hindlimb motor function, and spinal cord and serum injury biomarkers were recorded. NBO-U0126 pretreatment significantly decreased the incidence of DCS, improved motor function, and attenuated oxidative stress, inflammatory response, and apoptosis in both the spinal cord and serum. These results suggest that pretreatment with NBO and U0126 combined can effectively alleviate DCS spinal cord injury in rats by upregulating HSP32. This may lead to a more convenient approach for DCS injury control, using non-pressurized NBO instead of HBO.
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spelling doaj.art-53457e044aa9407796a9eb001b5841ed2022-12-21T22:45:45ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-06-011210.3389/fphys.2021.674430674430MEK1/2 Inhibition Synergistically Enhances the Preventive Effects of Normobaric Oxygen on Spinal Cord Injury in Decompression Sickness RatsQuan Zhou0Xiangyang Meng1Guoyang Huang2Hongjie Yi3Juan Zheng4Kun Zhang5Weigang Xu6Department of Diving and Hyperbaric Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, ChinaDepartment of Diving and Hyperbaric Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, ChinaDepartment of Diving and Hyperbaric Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, ChinaDepartment of Hyperbaric Oxygen, The First Affiliated Hospital, Naval Medical University, Shanghai, ChinaDepartment of Diving and Hyperbaric Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, ChinaDepartment of Diving and Hyperbaric Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, ChinaDepartment of Diving and Hyperbaric Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, ChinaA previous study from our team found that hyperbaric oxygen (HBO) pretreatment attenuated decompression sickness (DCS) spinal cord injury by upregulating heat shock protein 32 (HSP32) via the ROS/p38 MAPK pathway. Meanwhile, a MEK1/2-negative regulatory pathway was also activated to inhibit HSP32 overexpression. The purpose of this study was to determine if normobaric oxygen (NBO) might effectively induce HSP32 while concurrently inhibiting MEK1/2 and to observe any protective effects on spinal cord injury in DCS rats. The expression of HSP32 in spinal cord tissue was measured at 6, 12, 18, and 24 h following NBO and MEK1/2 inhibitor U0126 pretreatment. The peak time of HSP32 was observed at 12 h after simulated air diving. Subsequently, signs of DCS, hindlimb motor function, and spinal cord and serum injury biomarkers were recorded. NBO-U0126 pretreatment significantly decreased the incidence of DCS, improved motor function, and attenuated oxidative stress, inflammatory response, and apoptosis in both the spinal cord and serum. These results suggest that pretreatment with NBO and U0126 combined can effectively alleviate DCS spinal cord injury in rats by upregulating HSP32. This may lead to a more convenient approach for DCS injury control, using non-pressurized NBO instead of HBO.https://www.frontiersin.org/articles/10.3389/fphys.2021.674430/fulldecompression sicknessspinal cord injurynormobaric oxygenMEK1/2U0126heat shock protein 32
spellingShingle Quan Zhou
Xiangyang Meng
Guoyang Huang
Hongjie Yi
Juan Zheng
Kun Zhang
Weigang Xu
MEK1/2 Inhibition Synergistically Enhances the Preventive Effects of Normobaric Oxygen on Spinal Cord Injury in Decompression Sickness Rats
Frontiers in Physiology
decompression sickness
spinal cord injury
normobaric oxygen
MEK1/2
U0126
heat shock protein 32
title MEK1/2 Inhibition Synergistically Enhances the Preventive Effects of Normobaric Oxygen on Spinal Cord Injury in Decompression Sickness Rats
title_full MEK1/2 Inhibition Synergistically Enhances the Preventive Effects of Normobaric Oxygen on Spinal Cord Injury in Decompression Sickness Rats
title_fullStr MEK1/2 Inhibition Synergistically Enhances the Preventive Effects of Normobaric Oxygen on Spinal Cord Injury in Decompression Sickness Rats
title_full_unstemmed MEK1/2 Inhibition Synergistically Enhances the Preventive Effects of Normobaric Oxygen on Spinal Cord Injury in Decompression Sickness Rats
title_short MEK1/2 Inhibition Synergistically Enhances the Preventive Effects of Normobaric Oxygen on Spinal Cord Injury in Decompression Sickness Rats
title_sort mek1 2 inhibition synergistically enhances the preventive effects of normobaric oxygen on spinal cord injury in decompression sickness rats
topic decompression sickness
spinal cord injury
normobaric oxygen
MEK1/2
U0126
heat shock protein 32
url https://www.frontiersin.org/articles/10.3389/fphys.2021.674430/full
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