Purpurin inhibits adipocyte-derived leucine aminopeptidase and angiogenesis in a zebrafish model

Hyomi Park, Joong Sup Shim, Beom Seok Kim, Hye Jin Jung, Tae Lin Huh, Ho Jeong Kwon

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 K i value of 20 M. 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.

Original languageEnglish
Pages (from-to)561-567
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume450
Issue number1
DOIs
Publication statusPublished - 2014 Jul 18

Fingerprint

Leucyl Aminopeptidase
Zebrafish
Adipocytes
Metalloproteases
Biological Products
Zinc
Screening
Small Molecule Libraries
CD13 Antigens
Endothelial cells
Human Umbilical Vein Endothelial Cells
Vascular Endothelial Growth Factor A
Toxicity
purpurin
Assays
Embryonic Structures
Enzymes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Park, Hyomi ; Shim, Joong Sup ; Kim, Beom Seok ; Jung, Hye Jin ; Huh, Tae Lin ; Kwon, Ho Jeong. / Purpurin inhibits adipocyte-derived leucine aminopeptidase and angiogenesis in a zebrafish model. In: Biochemical and Biophysical Research Communications. 2014 ; Vol. 450, No. 1. pp. 561-567.
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Purpurin inhibits adipocyte-derived leucine aminopeptidase and angiogenesis in a zebrafish model. / Park, Hyomi; Shim, Joong Sup; Kim, Beom Seok; Jung, Hye Jin; Huh, Tae Lin; Kwon, Ho Jeong.

In: Biochemical and Biophysical Research Communications, Vol. 450, No. 1, 18.07.2014, p. 561-567.

Research output: Contribution to journalArticle

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