Covalent Modification of Phosphatidylethanolamine by Benzyl Isothiocyanate and the Resultant Generation of Ethanolamine Adduct as Its Metabolite

Toshiyuki Nakamura, Miho Hirakawa, Yoshimasa Nakamura, Akari Ishisaka, Noritoshi Kitamoto, Akira Murakami, Yoji Kato

Research output: Contribution to journalArticle

Abstract

Benzyl isothiocyanate (BITC), a dietary isothiocyanate (ITC) derived from cruciferous vegetables, has anticancer properties. It is believed that the ITC moiety (-N=C=S) that reacts predominantly with thiol compounds plays a central role in triggering the activities resulting from these properties. Recent studies have demonstrated that ITCs also covalently modify amino moieties in a protein. In this study, we examined the chemical reaction between BITC and the aminophospholipid, phosphatidylethanolamine (PE), in the cell membrane or lipoprotein particle. To detect the BITC-modified PE, the bond between ethanolamine (EA) and phosphatidic acid in PE was cleaved using phospholipase D to form the BITC-EA adduct, which was then measured. BITC-EA was detected from the BITC-treated unilamellar liposome and low-density lipoprotein even with only a few micromoles of BITC treatment, suggesting that BITC might react with not only a thiol/amino group of a protein but also an amino moiety of an aminophospholipid. Moreover, after incorporating BITC-PE included in the liposomes into the cultured cells or after direct exposure of BITC to the cells, free BITC-EA was excreted and accumulated in the medium in a time-dependent manner. It indicates that an intracellular enzyme catalyzes the cleavage of BITC-PE to produce BITC-EA. Because the ITC-amine adduct is stable, the ITC-EA adduct could be a promising indicator of ITC exposure in vivo.

Original languageEnglish
Pages (from-to)638-644
Number of pages7
JournalChemical Research in Toxicology
Volume32
Issue number4
DOIs
Publication statusPublished - Apr 15 2019

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Ethanolamine
Metabolites
Sulfhydryl Compounds
phosphatidylethanolamine
benzyl isothiocyanate
Phospholipase D
Unilamellar Liposomes
Phosphatidic Acids
Vegetables
Cell membranes
LDL Lipoproteins
Liposomes
Lipoproteins
Amines
Chemical reactions
Cultured Cells
Proteins

ASJC Scopus subject areas

  • Toxicology

Cite this

Covalent Modification of Phosphatidylethanolamine by Benzyl Isothiocyanate and the Resultant Generation of Ethanolamine Adduct as Its Metabolite. / Nakamura, Toshiyuki; Hirakawa, Miho; Nakamura, Yoshimasa; Ishisaka, Akari; Kitamoto, Noritoshi; Murakami, Akira; Kato, Yoji.

In: Chemical Research in Toxicology, Vol. 32, No. 4, 15.04.2019, p. 638-644.

Research output: Contribution to journalArticle

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