ZFIN ID: ZDB-PUB-140615-6
Purpurin inhibits adipocyte-derived leucine aminopeptidase and angiogenesis in a zebrafish model
Park, H., Shim, J.S., Kim, B.S., Jung, H.J., Huh, T.L., Kwon, H.J.
Date: 2014
Source: Biochemical and Biophysical Research Communications   450(1): 561-7 (Journal)
Registered Authors: Huh, Tae-Lin
Keywords: Adipocyte-derived leucine aminopeptidase (A-LAP), Angiogenesis, Drug screening, Purpurin
MeSH Terms:
  • Adipocytes/enzymology*
  • Animals
  • Anthraquinones/pharmacology*
  • Cell Survival/drug effects
  • Cells, Cultured
  • Endothelial Cells/drug effects
  • Endothelial Cells/physiology*
  • Enzyme Inhibitors/pharmacology
  • Humans
  • Leucyl Aminopeptidase/antagonists & inhibitors*
  • Leucyl Aminopeptidase/metabolism*
  • Models, Animal
  • Neovascularization, Physiologic/drug effects
  • Neovascularization, Physiologic/physiology*
  • Zebrafish/physiology*
PubMed: 24928393 Full text @ Biochem. Biophys. Res. Commun.
ABSTRACT
Adipocyte-derived leucine aminopeptidase (A-LAP) is a novel member of the M1 family of zinc metallopeptidases, which has been reported to play a crucial role in angiogenesis. In the present study, we conducted a target-based screening of natural products and synthetic chemical libraries using the purified enzyme to search novel inhibitors of A-LAP. Amongst several hits isolated, a natural product purpurin was identified as one of the most potent inhibitors of A-LAP from the screening. In vitro enzymatic analyses demonstrated that purpurin inhibited A-LAP activity in a non-competitive manner with a Ki value of 20 μM. In addition, purpurin showed a strong selectivity toward A-LAP versus another member of M1 family of zinc metallopeptidase, aminopeptidase N (APN). In angiogenesis assays, purpurin inhibited the vascular endothelial growth factor (VEGF)-induced invasion and tube formation of human umbilical vein endothelial cells (HUVEC). Moreover, purpurin inhibited in vivo angiogenesis in zebrafish embryo without toxicity. These data demonstrate that purpurin is a novel specific inhibitor of A-LAP and could be developed as a new anti-angiogenic agent.
ADDITIONAL INFORMATION No data available