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Copper induce zebrafish retinal developmental defects via triggering stresses and apoptosis

视网膜 细胞生物学 斑马鱼 ATP7A型 生物 视网膜变性 活性氧 线粒体 化学 生物化学 运输机 基因
作者
Guang Zhao,Haojie Sun,Ting Zhang,Jing‐Xia Liu
出处
期刊:Cell Communication and Signaling [Springer Nature]
卷期号:18 (1) 被引量:49
标识
DOI:10.1186/s12964-020-00548-3
摘要

Abstract Background The disorder of copper homeostasis is linked with disease and developmental defects, and excess copper_nanoparticles (CuNPs) and ion (Cu 2+ ) will induce developmental malformation and disease in organisms. However, little knowledge is available regarding its potential regulation mechanisms, and little study links excess copper with retinal developmental malformation and disease. Methods Embryos were stressed with copper (CuNPs and Cu 2+ ), and cell proliferation and apoptosis assays, reactive oxygen species (ROS) and endoplasmic reticulum (ER) signaling detections, and genetic mutants cox17 −/− and atp7a −/− application, were used to evaluate copper induced retinal developmental malformation and the underlying genetic and biological regulating mechanisms. Results Copper reduced retinal cells and down-regulated expression of retinal genes, damaged the structures of ER and mitochondria in retinal cells, up-regulated unfold protein responses (UPR) and ROS, and increased apoptosis in copper-stressed retinal cells. The copper induced retinal defects could be significantly neutralized by ROS scavengers reduced Glutathione (GSH) & N-acetylcysteine (NAC) and ER stress inhibitor 4- phenylbutyric acid (PBA). Blocking the transportation of copper to mitochondria, or to trans-Golgi network and to be exported into plasma, by deleting gene cox17 or atp7a , could alleviate retinal developmental defects in embryos under copper stresses. Conclusions This is probably the first report to reveal that copper nanoparticles and ions induce retinal developmental defects via upregulating UPR and ROS, leading to apoptosis in zebrafish embryonic retinal cells. Integrated function of copper transporter (Cox17 and Atp7a) is necessary for copper induced retinal defects. Graphical abstract
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