title: Hepcidin is involved in iron regulation in the ischemic brain.
abstract: Oxidative stress plays an important role in neuronal injuries caused by cerebral ischemia. It is well established that free iron increases significantly during ischemia and is responsible for oxidative damage in the brain. However, the mechanism of this ischemia-induced increase in iron is not completely understood. In this report, the middle cerebral artery occlusion (MCAO) rat model was performed and the mechanism of iron accumulation in cerebral ischemia-reperfusion was studied. The expression of L-ferritin was significantly increased in the cerebral cortex, hippocampus, and striatum on the ischemic side, whereas H-ferritin was reduced in the striatum and increased in the cerebral cortex and hippocampus. The expression level of the iron-export protein ferroportin1 (FPN1) significantly decreased, while the expression of transferrin receptor 1 (TfR1) was increased. In order to elucidate the mechanisms of FPN1 regulation, we studied the expression of the key regulator of FPN1, hepcidin. We observed that the hepcidin level was significantly elevated in the ischemic side of the brain. Knockdown hepcidin repressed the increasing of L-ferritin and decreasing of FPN1 invoked by ischemia-reperfusion. The results indicate that hepcidin is an important contributor to iron overload in cerebral ischemia. Furthermore, our results demonstrated that the levels of hypoxia-inducible factor-1α (HIF-1α) were significantly higher in the cerebral cortex, hippocampus and striatum on the ischemic side; therefore, the HIF-1α-mediated TfR1 expression may be another contributor to the iron overload in the ischemia-reperfusion brain.
authors.affiliation: Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.forename: Cai-Zhen
authors.initials: CZ
authors.lastname: Yan
authors.forename: Honglian
authors.initials: H
authors.lastname: Shi
authors.forename: Ya-Shuo
authors.initials: YS
authors.lastname: Zhao
authors.forename: Shi-Yang
authors.initials: SY
authors.lastname: Chang
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.forename: Wen-Shuang
authors.initials: WS
authors.lastname: Wu
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Zhao
authors.forename: Yan-Zhong
authors.initials: YZ
authors.lastname: Chang
authors.forename: Xiang-Lin
authors.initials: XL
authors.lastname: Duan
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D064451:Hepcidins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000150:complications / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications; D015854:Up-Regulation; D000098742:Ferroportin
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C579599:Hamp protein, mouse; C578703:Hamp protein, rat; D064451:Hepcidins; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse; D000098742:Ferroportin; D005293:Ferritins; D007501:Iron