title: Copper elevated embryonic hemoglobin through reactive oxygen species during zebrafish erythrogenesis.
abstract: Copper, as an essential trace mineral, can cause diseases such as childhood leukemia at excess levels, but has been applied in anemia therapy for a long time. However, few reports have studied its role during hematopoiesis at the molecular level in an animal model. In this study, by microarray, qRT-PCR, whole-mount in situ hybridization and O-dianisidine staining detections, we revealed the increased expression of hemoglobin in copper-exposed embryos. Secondly, we found that copper-exposed embryos exhibited high levels of reactive oxygen species (ROS), and genes in oxygen binding and oxygen transporting were up-regulated in the embryos. Finally, we found that ROS scavengers NAC, GSH, and DMTU not only inhibited in vivo ROS levels induced by copper, but also significantly decreased high expression of hemoglobin back to almost normal levels in copper exposed embryos, and also helped with copper elimination from the embryos. Our data first demonstrated that ROS mediated copper induced hemoglobin expression in vertebrates, partly revealing the underlying molecular mechanism of copper therapy for anemia. Moreover, we revealed that copper homeostasis was broken by its induced ROS and ROS helped with copper overloading in the body, which could be applied as a novel therapy target for copper-caused diseases.
authors.affiliation: College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: ameychow@yahoo.com.
authors.forename: Xin-Ying
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: zting@webmail.hzau.edu.cn.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: renlong21@163.com.
authors.forename: Long
authors.initials: L
authors.lastname: Ren
authors.affiliation: College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: 357787519@qq.com.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Wu
authors.affiliation: College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: wangwm@mail.hzau.edu.cn.
authors.forename: Weimin
authors.initials: W
authors.lastname: Wang
authors.affiliation: College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China; Collaborative Innovation Center for Efficient and Health Production of Fisheries in Hunan Province, Hunan, Changde 415000, China. Electronic address: ichliu@mail.hzau.edu.cn.
authors.forename: Jing-Xia
authors.initials: JX
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003300:Copper / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism*; D013058:Mass Spectrometry; D046228:Microarray Analysis; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D017382:Reactive Oxygen Species; D014874:Water Pollutants, Chemical; D003300:Copper
keywords: Copper; Hemoglobin; Reactive oxygen species (ROS); Scavengers