Hepcidin Promoted Ferroptosis through Iron Metabolism which Is Associated with DMT1 Signaling Activation in Early Brain Injury following Subarachnoid Hemorrhage.
Hepcidin Promoted Ferroptosis through Iron Metabolism which Is Associated with DMT1 Signaling Activation in Early Brain Injury following Subarachnoid Hemorrhage.
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铁调素通过铁代谢促进铁死亡，铁代谢与蛛网膜下腔出血后早期脑损伤中 DMT1 信号激活相关
DOI：
10.1155/2021/9800794
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发表时间：
2021
影响因子：
--
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Zhang H;Ostrowski R;Jiang D;Zhao Q;Liang Y;Che X;Zhao J;Xiang X;Qin W;He Z
Iron metabolism disturbances play an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH), and hepcidin largely influences iron metabolism. Importantly, iron metabolism may be associated with ferroptosis, recently a nonapoptotic iron-dependent form of cell death that may have a great impact on brain injury after SAH. We investigated hepcidin on iron metabolism and ferroptosis involving divalent metal transporter 1 (DMT1), and ferroportin-1 (FPN1) in a rat model of SAH. Male Sprague-Dawley rats were subjected to the endovascular perforation to induce SAH, and treated with heparin (inhibitor of hepcidin), or oncostatin M (OSM, inducer of hepcidin), or ebselen (inhibitor of DMT1) by intracerebroventricular injections. Hepcidin, DMT1, FPN1 and glutathione peroxidase 4 (GPX4), were detected by western blot and immunofluorescence. Iron metabolism was detected through Perl's iron staining and iron content assay. Ferroptosis, the ROS production, lipid peroxidation (LPO) was evaluated by monitoring methane dicarboxylic aldehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPX4) activity, and transmission electron microscopy. Neurological deficit scores, Evans blue staining and brain water content were also determined to detect EBI 72 h after SAH. Our results showed that inhibition of DMT1 by ebselen could suppress iron accumulation and lipid peroxidation, and thereby alleviate ferroptosis and EBI in SAH rats. Heparin downregulated the expression of hepcidin and DMT1, increased FPN1, and exerted protective effects that were equivalent to those of ebselen on ferroptosis and EBI. In addition, OSM increased the expression of hepcidin and DMT1, decreased FPN1, and aggravated ferroptosis and EBI, while the effect on ferroptosis was reversed by ebselen. Therefore, the study revealed that hepcidin could regulate iron metabolism and contribute to ferroptosis via DMT1 signaling activation in rats with EBI after SAH.
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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：
2.6
作者：
Kawabata, Hiroshi;Uchiyama, Tatsuki;Takaori-Kondo, Akifumi
通讯作者：
Takaori-Kondo, Akifumi
影响因子：
6.9
作者：
Fujii, Mutsumi;Yan, Junhao;Rolland, William B.;Soejima, Yoshiteru;Caner, Basak;Zhang, John H.
通讯作者：
Zhang, John H.
影响因子：
2.9
作者：
Magtanong, Leslie;Dixon, Scott J.
通讯作者：
Dixon, Scott J.
铁调素通过下调铁超载大鼠的铁转运蛋白来抑制脑铁积累
影响因子：
5.1
作者：
Du, Fang;Qian, Zhong-Ming;Ke, Ya
通讯作者：
Ke, Ya