Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4.
Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4.
复制标题
Liproxstatin-1 是一种通过抑制谷胱甘肽过氧化物酶 4 诱导的少突胶质细胞铁死亡的有效抑制剂。
DOI：
10.4103/1673-5374.293157
复制
发表时间：
2021-03
影响因子：
6.1
通讯作者：
Feng SQ
中科院分区：
文献类型：
--
作者：
Fan BY;Pang YL;Li WX;Zhao CX;Zhang Y;Wang X;Ning GZ;Kong XH;Liu C;Yao X;Feng SQ
我们以往的研究表明，铁下垂在脊髓损伤的急性和亚急性期起着重要作用。高细胞内铁水平和低谷胱甘肽水平使少突胶质细胞在中枢神经系统创伤后容易发生细胞死亡。在这项研究中，我们建立了一个少突胶质细胞（OLN-93细胞系）模型的铁凋亡的RSL-3，谷胱甘肽过氧化物酶4（GPX 4）的抑制剂。RSL-3显著增加细胞内活性氧和丙二醛的浓度。RSL-3还抑制主要的抗铁凋亡途径，即，SLC 7A 11/谷胱甘肽/谷胱甘肽过氧化物酶4（xCT/GSH/GPX 4），和下调的酰基辅酶A合成酶长链家族成员4。此外，我们评估了几种化合物从铁凋亡中拯救少突胶质细胞的能力。利司他汀-1比依达拉奉或去铁胺更有效。Lipostatin-1不仅能抑制线粒体脂质过氧化反应，还能恢复GSH、GPX 4和铁凋亡抑制蛋白1的表达。这些发现表明GPX 4抑制诱导少突胶质细胞中的铁凋亡，并且livestatin-1是铁凋亡的有效抑制剂。因此，livestatin-1可能是一种很有前途的治疗中枢神经系统疾病的药物。
Our previous studies showed that ferroptosis plays an important role in the acute and subacute stages of spinal cord injury. High intracellular iron levels and low glutathione levels make oligodendrocytes vulnerable to cell death after central nervous system trauma. In this study, we established an oligodendrocyte (OLN-93 cell line) model of ferroptosis induced by RSL-3, an inhibitor of glutathione peroxidase 4 (GPX4). RSL-3 significantly increased intracellular concentrations of reactive oxygen species and malondialdehyde. RSL-3 also inhibited the main anti-ferroptosis pathway, i.e., SLC7A11/glutathione/glutathione peroxidase 4 (xCT/GSH/GPX4), and downregulated acyl-coenzyme A synthetase long chain family member 4. Furthermore, we evaluated the ability of several compounds to rescue oligodendrocytes from ferroptosis. Liproxstatin-1 was more potent than edaravone or deferoxamine. Liproxstatin-1 not only inhibited mitochondrial lipid peroxidation, but also restored the expression of GSH, GPX4 and ferroptosis suppressor protein 1. These findings suggest that GPX4 inhibition induces ferroptosis in oligodendrocytes, and that liproxstatin-1 is a potent inhibitor of ferroptosis. Therefore, liproxstatin-1 may be a promising drug for the treatment of central nervous system diseases.
登录
查看更多内容
ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
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：
14.8
作者：
Gaschler MM;Andia AA;Liu H;Csuka JM;Hurlocker B;Vaiana CA;Heindel DW;Zuckerman DS;Bos PH;Reznik E;Ye LF;Tyurina YY;Lin AJ;Shchepinov MS;Chan AY;Peguero-Pereira E;Fomich MA;Daniels JD;Bekish AV;Shmanai VV;Kagan VE;Mahal LK;Woerpel KA;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
5.6
作者：
Sui, Xinbing;Zhang, Ruonan;Xie, Tian
通讯作者：
Xie, Tian
影响因子：
21.3
作者：
Friedmann Angeli JP;Schneider M;Proneth B;Tyurina YY;Tyurin VA;Hammond VJ;Herbach N;Aichler M;Walch A;Eggenhofer E;Basavarajappa D;Rådmark O;Kobayashi S;Seibt T;Beck H;Neff F;Esposito I;Wanke R;Förster H;Yefremova O;Heinrichmeyer M;Bornkamm GW;Geissler EK;Thomas SB;Stockwell BR;O'Donnell VB;Kagan VE;Schick JA;Conrad M
通讯作者：
Conrad M