Ferroptosis in oligodendrocyte progenitor cells mediates white matter injury after hemorrhagic stroke.
Ferroptosis in oligodendrocyte progenitor cells mediates white matter injury after hemorrhagic stroke.
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少突胶质细胞祖细胞中的铁死亡介导出血性中风后的白质损伤。
DOI：
10.1038/s41419-022-04712-0
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发表时间：
2022-03-23
影响因子：
9
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Shen D;Wu W;Liu J;Lan T;Xiao Z;Gai K;Hu L;Luo Z;Wei C;Wang X;Lu Y;Wang Y;Zhang C;Wang P;Zuo Z;Yang F;Li Q
少突胶质细胞祖细胞（OPCs）在发育和中枢神经系统疾病后分化为产生髓鞘的成熟少突胶质细胞，并包裹生长或脱髓鞘的轴突。由于OPCs的细胞死亡或未分化而导致的髓鞘再生失败会导致严重的神经功能缺损和运动功能障碍。然而，如何防止OPCs的细胞死亡仍然知之甚少，特别是在出血性疾病中。在本研究中，我们将自体血注射到小鼠侧脑室，以研究在体条件下血管紧张素Ⅱ诱导的OPC细胞死亡。脑室内出血后胼胝体髓鞘的完整性被破坏，通过磁共振成像、免疫染色和透射电子显微镜进行评估。与严重的去甲基化一致，我们观察到脑室周围区域的少突胶质细胞系大量细胞死亡。此外，通过RNA-seq分析，我们发现铁凋亡是Hemin诱导OPC死亡的主要细胞死亡形式，其机制是谷胱甘肽过氧化物酶4活性降低导致脂质过氧化物积累。此外，抑制铁凋亡在体外挽救OPC细胞死亡，并在体内减弱IVH诱导的白色损伤，促进神经功能的恢复。这些数据表明，铁凋亡是出血性中风中OPC细胞死亡的一种重要形式，拯救铁凋亡的OPC可以作为中风和相关疾病的治疗靶点。
Oligodendrocyte progenitor cells (OPCs) differentiate to myelin-producing mature oligodendrocytes and enwrap growing or demyelinated axons during development and post central nervous diseases. Failure of remyelination owing to cell death or undifferentiation of OPCs contributes to severe neurologic deficits and motor dysfunction. However, how to prevent the cell death of OPCs is still poorly understood, especially in hemorrhagic diseases. In the current study, we injected autologous blood into the mouse lateral ventricular to study the hemorrhage-induced OPC cell death in vivo. The integrity of the myelin sheath of the corpus callosum was disrupted post intraventricular hemorrhage (IVH) assessed by using magnetic resonance imaging, immunostaining, and transmission electron microscopy. Consistent with the severe demethylation, we observed massive cell death of oligodendrocyte lineages in the periventricular area. In addition, we found that ferroptosis is the major cell death form in Hemin-induced OPC death by using RNA-seq analysis, and the mechanism was glutathione peroxidase 4 activity reduction-resulted lipid peroxide accumulation. Furthermore, inhibition of ferroptosis rescued OPC cell death in vitro, and in vivo attenuated IVH-induced white matter injury and promoted recovery of neurological function. These data demonstrate that ferroptosis is an essential form of OPC cell death in hemorrhagic stroke, and rescuing ferroptotic OPCs could serve as a therapeutic target for stroke and related diseases.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
3.4
作者：
Li Q;Weiland A;Chen X;Lan X;Han X;Durham F;Liu X;Wan J;Ziai WC;Hanley DF;Wang J
通讯作者：
Wang J
DOI：
10.1038/s41582-020-00447-8
发表时间：
2021-04
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Ballabh P;de Vries LS
通讯作者：
de Vries LS
影响因子：
5.3
作者：
Jhelum, Priya;Santos-Nogueira, Eva;David, Samuel
通讯作者：
David, Samuel
铁死亡导致全视网膜间隙缺陷小鼠的光感受器变性
DOI：
10.1074/jbc.ra120.015779
发表时间：
2021-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Chen C;Chen J;Wang Y;Liu Z;Wu Y
通讯作者：
Wu Y