Identification of lysophosphatidylthreonine with an aromatic fatty acid surrogate as a potent inducer of mast cell degranulation

Takayuki Kishi, Hiroki Kawana, Misa Sayama, Kumiko Makide, Asuka Inoue, Yuko Otani, Tomohiko Ohwada, Junken Aoki

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Upon various stimulations, mast cells (MCs) release a wide variety of chemical mediators stored in their cytoplasmic granules, which then initiates subsequent allergic reactions. Lysophosphatidylserine (LysoPS), a kind of lysophospholipid, potentiates the histamine release from MCs triggered by antigen stimulation. We previously showed through structure-activity studies of LysoPS analogs that LysoPS with a methyl group at the carbon of the serine residue, i.e., lysophosphatidylthreonine (LysoPT), is extremely potent in stimulating the MC degranulation. In this study, as our continuing study to identify more potent LysoPS analogs, we developed LysoPS analogs with fatty acid surrogates. We found that the substitution of oleic acid to an aromatic fatty acid surrogate (C3-pH-p-O-C11) in 2-deoxy-1-LysoPS resulted in significant increase in the ability to induce MCs degranulation compared with 2-deoxy-1-LysoPS with oleic acid. Conversion of the serine residue into the threonine residue further increased the activity of MC degranulation both in vitro and in vivo. The resulting super agonist, 2-deoxy-LysoPT with C3-pH-p-O-C11, will be a useful tool to elucidate the mechanisms of stimulatory effect of LysoPS on MC degranulation.

Original languageEnglish
Pages (from-to)346-351
Number of pages6
JournalBiochemistry and Biophysics Reports
Volume8
DOIs
Publication statusPublished - 2016 Dec 1

Keywords

  • Degranulation
  • Lysophosphatidylserine
  • Lysophospholipid
  • Mast cell
  • Receptor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Fingerprint Dive into the research topics of 'Identification of lysophosphatidylthreonine with an aromatic fatty acid surrogate as a potent inducer of mast cell degranulation'. Together they form a unique fingerprint.

Cite this