Ferroptosis suppressor protein 1 regulated oligodendrocytes ferroptosis rescued by idebenone in spinal cord injury

被引：3

作者：

Fan, Baoyou ^{[1
,2
]}

Liu, Derong ^{[1
,2
]}

Qin, Jia ^{[3
]}

Shi, Zhongju ^{[1
,2
]}

Hu, Zicheng ^{[1
,2
]}

Gao, Xiang ^{[1
,2
]}

Ren, Yifei ^{[1
,2
]}

Zhao, Pengtian ^{[1
,2
]}

Chen, Xiaoyang ^{[1
,2
]}

Ren, Yiming ^{[1
,2
]}

Ning, Guangzhi ^{[1
,2
]}

Liu, Tao ^{[1
,2
]}

Feng, Shiqing ^{[1
,2
]}

机构：

[1] Tianjin Med Univ Gen Hosp, Dept Othopaed, 154 Anshan Rd, Tianjin 300052, Peoples R China

[2] Tianjin Med Univ Gen Hosp, Dept Orthoped, Tianjin Key Lab Spine & Spinal Cord Injury, Int Sci & Technol Cooperat Base Spinal Cord Injury, Tianjin, Peoples R China

[3] Sun Yat Sen Univ, Dept Orthoped Surg, Affiliated Hosp 1, Guizhou Hosp, 58 Zhongshan Er Rd, Guangzhou 510080, Guangdong, Peoples R China

来源：

FREE RADICAL BIOLOGY AND MEDICINE | 2025年 / 227卷

基金：

中国国家自然科学基金;

关键词：

FSP1; COQ10; Idebenone; Ferroptosis; Spinal cord injury; OXIDOREDUCTASE; INHIBITION; NAD(P)H;

D O I：

10.1016/j.freeradbiomed.2024.11.052

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Ferroptosis has been demonstrated to be involved in the progression of spinal cord injury (SCI). Ferroptosis suppressor protein 1 (FSP1) can inhibit ferroptosis in parallel with Glutathione peroxidase 4 (GPX4). However, the role of FSP1 in the pathogenesis of spinal cord injury is unclear. The protein and gene levels of FSP1 were found to be downregulated during both the acute and subacute stages after SCI. In addition to regulating ferroptosis by mediating CoQ, FSP1 also influences ferroptosis sensitivity by modulating cellular homeostasis and the metal ion response system, as demonstrated by FSP1 knockdown experiments. Furthermore, Idebenone (IDE) was identified as a ferroptosis inhibitor. IDE was shown to inhibit reactive oxygen species (ROS) and restore the expression of GPX4 and xCT, thereby suppressing ferroptosis of oligodendrocytes, even when FSP1 was knocked down. In vivo results indicated that IDE could effectively rescue oligodendrocytes and neurons from ferroptosis, promoting myelination of the injured spinal cord and facilitating tissue repair and functional recovery. This study provides a novel strategy for repairing SCI through the regulation of FSP1 in ferroptosis.

引用

页码：129 / 142

页数：14

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