ISRIB improves white matter injury following TBI by inhibiting NCOA4-mediated ferritinophagy

白质 创伤性脑损伤 神经保护 共域化 铁蛋白 医学 内科学 生物 神经科学 磁共振成像 精神科 放射科
作者
Wenzhu Zhou,Yidan Liang,Xinyu Liao,Luyao Tong,Weihong Du,Wenqiao Fu,Shanshan Tian,Yongbing Deng,Xue Jiang
出处
期刊:Neurochemistry International [Elsevier BV]
卷期号:177: 105744-105744 被引量:8
标识
DOI:10.1016/j.neuint.2024.105744
摘要

Traumatic brain injury (TBI) often results in persistent neurological dysfunction, which is closely associated with white matter injury. The mechanisms underlying white matter injury after TBI remain unclear. Ferritinophagy is a selective autophagic process that degrades ferritin and releases free iron, which may cause ferroptosis. Although ferroptosis has been demonstrated to be involved in TBI, it is unclear whether ferritinophagy triggers ferroptosis in TBI. Integrated stress response inhibitor (ISRIB) has neuroprotective properties. However, the effect of ISRIB on white matter after TBI remains uncertain. We aimed to investigate whether ferritinophagy was involved in white matter injury following TBI and whether ISRIB can mitigate white matter injury after TBI by inhibiting ferritinophagy. In this study, controlled cortical impact (CCI) was performed on rats to establish the TBI model. Ferritinophagy was measured by assessing the levels of nuclear receptor coactivator 4 (NCOA4), which regulates ferritinophagy, ferritin heavy chain 1(FTH1), LC3, ATG5, and FTH1 colocalization with LC3 in the white matter. Increased NCOA4 and decreased FTH1 were detected in our study. FTH1 colocalization with LC3 enhanced in the white matter after TBI, indicating that ferritinophagy was activated. Immunofluorescence co-localization results also suggested that ferritinophagy occurred in neurons and oligodendrocytes after TBI. Furthermore, ferroptosis was assessed by determining free iron content, MDA content, GSH content, and Perl's staining. The results showed that ferroptosis was suppressed by NCOA4 knockdown via shNCOA4 lentivirus infection, indicating that ferroptosis in TBI is triggered by ferritinophagy. Besides, NCOA4 deletion notably improved white matter injury following TBI, implying that ferritinophagy contributed to white matter injury. ISRIB treatment reduced the occurrence of ferritinophagy in neurons and oligodendrocytes, attenuated ferritinophagy-induced ferroptosis, and alleviated white matter injury. These findings suggest that NCOA4-mediated ferritinophagy is a critical mechanism underlying white matter injury after TBI. ISRIB holds promise as a therapeutic agent for this condition.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
windyhill完成签到,获得积分10
1秒前
鳗鱼紫萱完成签到,获得积分10
2秒前
我必定发nature关注了科研通微信公众号
2秒前
GG波波发布了新的文献求助10
3秒前
华仔应助晴云采纳,获得10
5秒前
快乐小狗完成签到 ,获得积分10
5秒前
珞珈完成签到,获得积分10
5秒前
Ya完成签到,获得积分10
5秒前
谦让文昊完成签到,获得积分10
6秒前
小红勇闯科研界完成签到,获得积分10
8秒前
科研通AI2S应助长安采纳,获得10
10秒前
10秒前
11秒前
Amber完成签到,获得积分10
11秒前
11秒前
teborlee完成签到,获得积分10
12秒前
xinxin完成签到,获得积分10
12秒前
SYLH应助鳗鱼鸽子采纳,获得10
12秒前
YY完成签到,获得积分10
13秒前
老德完成签到,获得积分10
13秒前
靓丽的熠彤完成签到,获得积分10
14秒前
深情海秋完成签到,获得积分10
14秒前
15秒前
歇洛克完成签到,获得积分10
16秒前
cao完成签到,获得积分20
16秒前
为你博弈完成签到,获得积分10
17秒前
17秒前
于情信芳完成签到,获得积分10
17秒前
庚小马发布了新的文献求助10
17秒前
淡然妙竹发布了新的文献求助10
18秒前
炒栗子发布了新的文献求助10
18秒前
晴云发布了新的文献求助10
18秒前
19秒前
PHW完成签到,获得积分10
19秒前
monly应助Fin2046采纳,获得30
20秒前
Hello应助JJG采纳,获得10
20秒前
李健的小迷弟应助WJH采纳,获得10
20秒前
22秒前
ty发布了新的文献求助10
22秒前
刘逸藩完成签到,获得积分10
22秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Research on Disturbance Rejection Control Algorithm for Aerial Operation Robots 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038569
求助须知:如何正确求助?哪些是违规求助? 3576279
关于积分的说明 11374944
捐赠科研通 3305979
什么是DOI,文献DOI怎么找? 1819354
邀请新用户注册赠送积分活动 892698
科研通“疑难数据库(出版商)”最低求助积分说明 815048