Ferroptosis inhibitor SRS 16-86 attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury

Yan Zhang; Chao Sun; Chenxi Zhao; Jian Hao; Yiling Zhang; Baoyou Fan; Bo Li; Huiquan Duan; Chang Liu; Xiaohong Kong; Ping Wu; Xue Yao; Shiqing Feng

doi:10.1016/j.brainres.2018.10.023

Ferroptosis inhibitor SRS 16-86 attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury

Yan Zhang, Chao Sun, Chenxi Zhao, Jian Hao, Yiling Zhang, Baoyou Fan, Bo Li, Huiquan Duan, Chang Liu, Xiaohong Kong, Ping Wu, Xue Yao, Shiqing Feng

Neuroscience & Cell

Research output: Contribution to journal › Article › peer-review

63 Scopus citations

Abstract

Cell death is a key issue in spinal cord secondary injury. Ferroptosis is recently discovered as an iron-dependent type of cell death that is distinct from other forms of cell death pathways such as apoptosis and necrosis. This research is aimed to investigate the role of ferroptosis in spinal cord injury (SCI) pathophysiology, and to explore the effectiveness of ferroptosis inhibitor on SCI. We examined the ferroptosis markers and the factors in a rat contusion SCI model. Seen from transmission electron microscopy (TEM) following SCI, mitochondria showed ferroptotic characteristic changes. Treatment with a ferroptosis inhibitor SRS 16-86 enhanced functional recovery after SCI through the upregulation of anti-ferroptosis factor GPX4, GSH and xCT, and the downregulation of the lipid peroxidation marker 4HNE. SRS 16-86 treatment alleviated astrogliosis and enhanced neuronal survival after SCI. The inflammatory cytokine levels (IL-1β, TNF-α and ICAM-1) were decreased significantly post SRS 16-86 treatment after SCI. These findings suggest strong correlation between ferroptosis and the secondary injury of SCI. The effectiveness of ferroptosis inhibitor SRS-16-86 on SCI repair leads to the identification of a novel therapeutic target for SCI.

Original language	English (US)
Pages (from-to)	48-57
Number of pages	10
Journal	Brain Research
Volume	1706
DOIs	https://doi.org/10.1016/j.brainres.2018.10.023
State	Published - Mar 1 2019

Keywords

Ferroptosis
Ferroptosis inhibitor
GPX4
Regulated cell death
Secondary injury
Spinal cord injury

ASJC Scopus subject areas

Neuroscience(all)
Molecular Biology
Clinical Neurology
Developmental Biology

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10.1016/j.brainres.2018.10.023

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@article{e47cf1ace0b1472ebcd9e9f1fdfd8ed9,

title = "Ferroptosis inhibitor SRS 16-86 attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury",

abstract = "Cell death is a key issue in spinal cord secondary injury. Ferroptosis is recently discovered as an iron-dependent type of cell death that is distinct from other forms of cell death pathways such as apoptosis and necrosis. This research is aimed to investigate the role of ferroptosis in spinal cord injury (SCI) pathophysiology, and to explore the effectiveness of ferroptosis inhibitor on SCI. We examined the ferroptosis markers and the factors in a rat contusion SCI model. Seen from transmission electron microscopy (TEM) following SCI, mitochondria showed ferroptotic characteristic changes. Treatment with a ferroptosis inhibitor SRS 16-86 enhanced functional recovery after SCI through the upregulation of anti-ferroptosis factor GPX4, GSH and xCT, and the downregulation of the lipid peroxidation marker 4HNE. SRS 16-86 treatment alleviated astrogliosis and enhanced neuronal survival after SCI. The inflammatory cytokine levels (IL-1β, TNF-α and ICAM-1) were decreased significantly post SRS 16-86 treatment after SCI. These findings suggest strong correlation between ferroptosis and the secondary injury of SCI. The effectiveness of ferroptosis inhibitor SRS-16-86 on SCI repair leads to the identification of a novel therapeutic target for SCI.",

keywords = "Ferroptosis, Ferroptosis inhibitor, GPX4, Regulated cell death, Secondary injury, Spinal cord injury",

author = "Yan Zhang and Chao Sun and Chenxi Zhao and Jian Hao and Yiling Zhang and Baoyou Fan and Bo Li and Huiquan Duan and Chang Liu and Xiaohong Kong and Ping Wu and Xue Yao and Shiqing Feng",

note = "Funding Information: We appreciate the critical review of Prof. Wise Young from W.M. Keck Center for Collaborative Neuroscience, Rutgers University. We thank the support of the following funding: NSFC program [grant number 81672171, 81330042, 81620108018, 81472070, 81772342], State Key Laboratory of Medicinal Chemical Biology (Nankai University), China [grant number 2017027]. Funding Information: We appreciate the critical review of Prof. Wise Young from W.M. Keck Center for Collaborative Neuroscience, Rutgers University. We thank the support of the following funding: NSFC program [grant number 81672171, 81330042 , 81620108018 , 81472070 , 81772342 ], State Key Laboratory of Medicinal Chemical Biology (Nankai University), China [grant number 2017027 ]. Publisher Copyright: {\textcopyright} 2018",

year = "2019",

month = mar,

day = "1",

doi = "10.1016/j.brainres.2018.10.023",

language = "English (US)",

volume = "1706",

pages = "48--57",

journal = "Brain Research",

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T1 - Ferroptosis inhibitor SRS 16-86 attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury

AU - Zhang, Yan

AU - Sun, Chao

AU - Zhao, Chenxi

AU - Hao, Jian

AU - Zhang, Yiling

AU - Fan, Baoyou

AU - Li, Bo

AU - Duan, Huiquan

AU - Liu, Chang

AU - Kong, Xiaohong

AU - Wu, Ping

AU - Yao, Xue

AU - Feng, Shiqing

N1 - Funding Information: We appreciate the critical review of Prof. Wise Young from W.M. Keck Center for Collaborative Neuroscience, Rutgers University. We thank the support of the following funding: NSFC program [grant number 81672171, 81330042, 81620108018, 81472070, 81772342], State Key Laboratory of Medicinal Chemical Biology (Nankai University), China [grant number 2017027]. Funding Information: We appreciate the critical review of Prof. Wise Young from W.M. Keck Center for Collaborative Neuroscience, Rutgers University. We thank the support of the following funding: NSFC program [grant number 81672171, 81330042 , 81620108018 , 81472070 , 81772342 ], State Key Laboratory of Medicinal Chemical Biology (Nankai University), China [grant number 2017027 ]. Publisher Copyright: © 2018

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Cell death is a key issue in spinal cord secondary injury. Ferroptosis is recently discovered as an iron-dependent type of cell death that is distinct from other forms of cell death pathways such as apoptosis and necrosis. This research is aimed to investigate the role of ferroptosis in spinal cord injury (SCI) pathophysiology, and to explore the effectiveness of ferroptosis inhibitor on SCI. We examined the ferroptosis markers and the factors in a rat contusion SCI model. Seen from transmission electron microscopy (TEM) following SCI, mitochondria showed ferroptotic characteristic changes. Treatment with a ferroptosis inhibitor SRS 16-86 enhanced functional recovery after SCI through the upregulation of anti-ferroptosis factor GPX4, GSH and xCT, and the downregulation of the lipid peroxidation marker 4HNE. SRS 16-86 treatment alleviated astrogliosis and enhanced neuronal survival after SCI. The inflammatory cytokine levels (IL-1β, TNF-α and ICAM-1) were decreased significantly post SRS 16-86 treatment after SCI. These findings suggest strong correlation between ferroptosis and the secondary injury of SCI. The effectiveness of ferroptosis inhibitor SRS-16-86 on SCI repair leads to the identification of a novel therapeutic target for SCI.

AB - Cell death is a key issue in spinal cord secondary injury. Ferroptosis is recently discovered as an iron-dependent type of cell death that is distinct from other forms of cell death pathways such as apoptosis and necrosis. This research is aimed to investigate the role of ferroptosis in spinal cord injury (SCI) pathophysiology, and to explore the effectiveness of ferroptosis inhibitor on SCI. We examined the ferroptosis markers and the factors in a rat contusion SCI model. Seen from transmission electron microscopy (TEM) following SCI, mitochondria showed ferroptotic characteristic changes. Treatment with a ferroptosis inhibitor SRS 16-86 enhanced functional recovery after SCI through the upregulation of anti-ferroptosis factor GPX4, GSH and xCT, and the downregulation of the lipid peroxidation marker 4HNE. SRS 16-86 treatment alleviated astrogliosis and enhanced neuronal survival after SCI. The inflammatory cytokine levels (IL-1β, TNF-α and ICAM-1) were decreased significantly post SRS 16-86 treatment after SCI. These findings suggest strong correlation between ferroptosis and the secondary injury of SCI. The effectiveness of ferroptosis inhibitor SRS-16-86 on SCI repair leads to the identification of a novel therapeutic target for SCI.

KW - Ferroptosis

KW - Ferroptosis inhibitor

KW - GPX4

KW - Regulated cell death

KW - Secondary injury

KW - Spinal cord injury

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DO - 10.1016/j.brainres.2018.10.023

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JO - Brain Research

JF - Brain Research

SN - 0006-8993

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Ferroptosis inhibitor SRS 16-86 attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury

Abstract

Keywords

ASJC Scopus subject areas

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