Fluorescence probes to detect lipid-derived radicals

Ken Ichi Yamada, Fumiya Mito, Yuta Matsuoka, Satsuki Ide, Kazushige Shikimachi, Ayano Fujiki, Daiki Kusakabe, Yuma Ishida, Masataka Enoki, Arisa Tada, Miyuki Ariyoshi, Toshihide Yamasaki, Mayumi Yamato

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Lipids and their metabolites are easily oxidized in chain reactions initiated by lipid radicals, forming lipid peroxidation products that include the electrophiles 4-hydroxynonenal and malondialdehyde. These markers can bind cellular macromolecules, causing inflammation, apoptosis and other damage. Methods to detect and neutralize the initiating radicals would provide insights into disease mechanisms and new therapeutic approaches. We describe the first high-sensitivity, specific fluorescence probe for lipid radicals, 2,2,6-Trimethyl-4-(4-nitrobenzo[1,2,5]oxadiazol-7-ylamino)-6-pentylpiperidine-1-oxyl (NBD-Pen). NBD-Pen directly detected lipid radicals in living cells by turn-on fluorescence. In a rat model of hepatic carcinoma induced by diethylnitrosamine (DEN), NBD-Pen detected lipid radical generation within 1 h of DEN administration. The lipid radical scavenging moiety of NBD-Pen decreased inflammation, apoptosis and oxidative stress markers at 24 h after DEN, and liver tumor development at 12 weeks. Thus, we have developed a novel fluorescence probe that provides imaging information about lipid radical generation and potential therapeutic benefits in vivo.

Original languageEnglish
Pages (from-to)608-613
Number of pages6
JournalNature Chemical Biology
Volume12
Issue number8
DOIs
Publication statusPublished - Aug 1 2016

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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