Identification of Protein Targets of 12/15-Lipoxygenase-Derived Lipid Electrophiles in Mouse Peritoneal Macrophages Using Omega-Alkynyl Fatty Acid

Yosuke Isobe, Yusuke Kawashima, Tomoaki Ishihara, Kenji Watanabe, Osamu Ohara, Makoto Arita

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The 12/15-lipoxygenase (12/15-LOX) enzyme introduces peroxyl groups, in a position-specific manner, into polyunsaturated fatty acids to form various kinds of bioactive lipid metabolites, including lipid-derived electrophiles (LDE). The resident peritoneal macrophage is the site of highest 12/15-LOX expression in the mouse. However, the role of the enzyme in the regulation of resident macrophages is not fully understood. Here, we describe a chemoproteomic method to identify the targets of enzymatically generated LDE. By treating mouse peritoneal macrophages with omega-alkynyl arachidonic acid (aAA), we identified a series of proteins adducted by LDE generated through a 12/15-LOX catalyzed reaction. Pathway analysis revealed a dramatic enrichment of proteins involved in energy metabolism and found that glycolytic flux and mitochondrial respiration were significantly affected by the expression of 12/15-LOX. Our findings thus highlight the utility of chemoproteomics using aAA for identifying intracellular targets of enzymatically generated LDE.

Original languageEnglish
Pages (from-to)887-893
Number of pages7
JournalACS Chemical Biology
Volume13
Issue number4
DOIs
Publication statusPublished - 2018 Apr 20

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Macrophages
Peritoneal Macrophages
Fatty Acids
Lipids
Proteins
Arachidonic Acid
Enzymes
Metabolites
Unsaturated Fatty Acids
Energy Metabolism
Respiration
12-15-lipoxygenase
Fluxes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Identification of Protein Targets of 12/15-Lipoxygenase-Derived Lipid Electrophiles in Mouse Peritoneal Macrophages Using Omega-Alkynyl Fatty Acid. / Isobe, Yosuke; Kawashima, Yusuke; Ishihara, Tomoaki; Watanabe, Kenji; Ohara, Osamu; Arita, Makoto.

In: ACS Chemical Biology, Vol. 13, No. 4, 20.04.2018, p. 887-893.

Research output: Contribution to journalArticle

Isobe, Yosuke ; Kawashima, Yusuke ; Ishihara, Tomoaki ; Watanabe, Kenji ; Ohara, Osamu ; Arita, Makoto. / Identification of Protein Targets of 12/15-Lipoxygenase-Derived Lipid Electrophiles in Mouse Peritoneal Macrophages Using Omega-Alkynyl Fatty Acid. In: ACS Chemical Biology. 2018 ; Vol. 13, No. 4. pp. 887-893.
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