The Oxidative Stress Effect Of Exogenetic Copper On Zebrafish Hematopoiesis

Copper is an essential trace mineral in human body,participating in biological synthesis processes as an enzyme.Metabolic disorder of copper can cause multiple deseases.As an important model animal,zebrafish(Danio rerio)is commonly used in ecological toxicology,developmental biology and molecular biology.Such as evaluating environmental stress factors and constructing pathology models.Our research studied the expressions of functional genes and the physiological metabolic regulation in zebrafish hematopoietic system and the physiological metabolic dysfunction caused by copper.By investigating the main effects and the underlying molecular mechanisms of copper ions on hematopoietic system and early embryonic development,the data here will provide the theoretical basis for expanding the study of copper metabolism and copper-related diseases.The main results are as follows:1.Effects of copper on zebrafish hemopoiesis.In this study,the effect of copper on zebrafish hemopoiesis was analyzed step by step.We revealed that copper induced expanded RBCs(red blood cells),but decreased the expressions of HSCs(hematopoietic stem cells)and of Notch and Wnt pathways at transcriptional level.In adult,copper increased cell differentiation in hematopoietic system,as well as increased RBCs,but reduced progenitor hematopoietic cells in kidney and PB(peripheral blood).All above observations demonstrate that exogenous copper disturbed the balance of zebrafish hematopoiesis,and destroied the development and regeneration of zebrafish embryonic hematopoiesis.2.Oxidative stress in zebrafish induced by copper.By microarray analysis,transcriptional level verification and ROS(Reactive Oxygen Species)content detection,it revealed that copper-exposed embryos exhibited high levels of ROS,and genes in oxygen binding and oxygen transporting were up-regulated.Furthermore,pretreatment of antioxidants not only can efficiently recover high expression of RBCs genes back to almost normal levels,but also can help with copper elimination.3.Copper and antioxidants affcted zebrafish hematopoiesis.Pretreatment of antioxidants can remove increased intracellular ROS,rescue copper-elevated RBCs synthesis.By genome-wide methylation analysis,it revealed that hypermethylation was observed enhanced in promoter regions of HSCs.All above demonstrate that exogenous copper elevated oxidative response,thereby enhanced the differentiation of hematopoietic system and disrupted the balance of copper metabolism.Moreover,exogenous antioxidants can effectively recover the increased RBCs and the decreased regeneration ability,as well as recover copper metabolism.Furthermore,the development and regeneration of hematopoietic regulated by oxidative stress progress may derived from methylation in promoter regions of HSCs.