PUBLICATION

Microinjecting recombinant rainbow trout Ea4-peptide of pro-IGF-I into zebrafish embryos causes abnormal development in heart, red blood cells, and vasculature

Authors
Chun, C.Z., and Chen, T.T.
ID
ZDB-PUB-060825-5
Date
2007
Source
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP   145(1): 39-44 (Journal)
Registered Authors
Chun, Chang Zoon
Keywords
rtEa4-peptide, Heart development, Hematopoiesis, Vasculogenesis
MeSH Terms
  • Animals
  • Blood Vessels/abnormalities*
  • Blood Vessels/drug effects
  • Blood Vessels/embryology*
  • DNA Primers
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian/abnormalities
  • Embryo, Nonmammalian/pathology
  • Embryo, Nonmammalian/physiology
  • Erythrocytes/drug effects*
  • Gene Expression Regulation, Developmental/drug effects
  • Heart/drug effects
  • Heart/embryology*
  • Heart Defects, Congenital/chemically induced
  • Heart Defects, Congenital/pathology
  • Humans
  • Insulin-Like Growth Factor I/administration & dosage
  • Insulin-Like Growth Factor I/chemistry
  • Insulin-Like Growth Factor I/pharmacology*
  • Microinjections
  • Oncorhynchus mykiss
  • Peptide Fragments/administration & dosage
  • Peptide Fragments/pharmacology*
  • Protein Precursors/administration & dosage
  • Protein Precursors/chemistry
  • Protein Precursors/pharmacology*
  • RNA, Messenger/biosynthesis
  • Recombinant Proteins/administration & dosage
  • Recombinant Proteins/pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Zebrafish
PubMed
16914384 Full text @ Comp. Biochem. Physiol. C Toxicol. Pharmacol.
Abstract
E-peptides and mature insulin-like growth factors (IGFs) are produced from pre-pro-IGFs during post-translational processing and co-secreted into the circulation. Previously, we reported that introduction of a transgene encoding the secreted form of rainbow trout (rt) Ea4-peptide or human (h) Eb-peptide into newly fertilized eggs of medaka (Oryzias latipes) and zebrafish (Danio rerio) resulted in developmental defects in heart, red blood cells and vasculature. In addition to vasculature and red blood cell developmental defects, multiple phenocopies of heart developmental defects categorized by developmental arrest at cardiomyocyte, heart tube and heart looping stages were also observed. These results raise a question of whether rtEa4- or hEb-peptide exerts pleiotropic inhibitory effects on heart, vasculature and red blood cell development in fish embryos. To answer this question, various amounts of recombinant rtEa4-peptide were microinjected into zebrafish eggs at 1.5, 2.5 and 5.5 h post-fertilization (hpf). Although a dose-dependent developmental defect in heart, vasculature and red blood cells was observed in embryos microinjected with rtEa4-peptide at 1.5 and 2.5 hpf, the heart development in all of the microinjected embryos was arrested at the cardiomyocyte stage. Furthermore, the mRNA levels of Nkx2.5, GATA5, VEGF, GATA1 and GATA2 genes in defective embryos were significantly reduced by rtEa4-peptide. These results confirm our previous findings that rtEa4- or hEb-peptide exhibits pleiotropic effects in inhibiting heart, vasculature and red blood cell development in zebrafish embryos.
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