PUBLICATION

Glycine exerts dose-dependent biphasic effects on vascular development of zebrafish embryos

Authors
Tsuji-Tamura, K., Sato, M., Fujita, M., Tamura, M.
ID
ZDB-PUB-200520-4
Date
2020
Source
Biochemical and Biophysical Research Communications   527(2): 539-544 (Journal)
Registered Authors
Fujita, Misato
Keywords
Angiogenesis, Glycine, NOS, VEGF, Zebrafish
MeSH Terms
  • Angiogenesis Inducing Agents/pharmacology*
  • Angiogenesis Inhibitors/pharmacology*
  • Animals
  • Blood Vessels/drug effects
  • Blood Vessels/embryology*
  • Embryo, Nonmammalian/blood supply
  • Embryo, Nonmammalian/drug effects*
  • Glycine/pharmacology*
  • Neovascularization, Physiologic/drug effects
  • Zebrafish/embryology*
PubMed
32423801 Full text @ Biochem. Biophys. Res. Commun.
Abstract
Glycine, a non-essential amino acid, is involved in both angiogenesis and anti-angiogenesis. We hypothesized that glycine would exert dose-dependent different effects on angiogenesis. In this study, we investigated the effects of a broad range of concentrations of glycine on vascular development using transgenic zebrafish Tg(fli1a:Myr-mCherry)ncv1 embryos. Effects of glycine transporter (GlyT) inhibitors (sarcosine and bitopertin) and a glycine receptor (GlyR) inhibitor (strychnine) were also examined in embryos in the absence or presence of glycine. After exposure to glycine and inhibitors, intersegmental vessels (ISVs) were observed by fluorescent microscopy. Low concentrations of glycine promoted the development of ISVs, whereas high concentrations reduced it. These effects of glycine could generally be reversed by treatment with GlyT and GlyR inhibitors. Furthermore, expressions of vascular endothelial growth factor (VEGF) (an angiogenic factor) and nitric oxide synthase (NOS) (an enzyme for nitric oxide synthesis) were associated with the dose-dependent effects of glycine. Our results suggest that glycine exerts dose-dependent biphasic effects on vascular development, which rely on GlyTs and GlyRs, and correlate with the expression of VEGF and NOS genes. At low concentrations, glycine acted as an angiogenic factor. In contrast, at high concentrations, glycine induced anti-angiogenesis. This evidence provides a novel insight into glycine as a unique target in angiogenic and anti-angiogenic therapy.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping