RRC ID 37875
Author Yamada K, Mito F, Matsuoka Y, Ide S, Shikimachi K, Fujiki A, Kusakabe D, Ishida Y, Enoki M, Tada A, Ariyoshi M, Yamasaki T, Yamato M.
Title Fluorescence probes to detect lipid-derived radicals.
Journal Nat Chem Biol
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.
Volume 12(8)
Pages 608-13
Published 2016-8-1
DOI 10.1038/nchembio.2105
PII nchembio.2105
PMID 27294322
MeSH 4-Chloro-7-nitrobenzofurazan / analogs & derivatives* 4-Chloro-7-nitrobenzofurazan / analysis 4-Chloro-7-nitrobenzofurazan / chemistry 4-Chloro-7-nitrobenzofurazan / pharmacology 4-Chloro-7-nitrobenzofurazan / therapeutic use Animals Apoptosis / drug effects Cell Line, Tumor Cyclic N-Oxides / analysis* Cyclic N-Oxides / chemistry* Cyclic N-Oxides / pharmacology Cyclic N-Oxides / therapeutic use Diethylnitrosamine Disease Models, Animal Fluorescent Dyes / analysis* Fluorescent Dyes / chemistry* Fluorescent Dyes / pharmacology Fluorescent Dyes / therapeutic use Free Radical Scavengers / analysis Free Radical Scavengers / chemistry Free Radical Scavengers / pharmacology Free Radical Scavengers / therapeutic use Free Radicals / analysis* Free Radicals / chemistry Free Radicals / metabolism Inflammation / prevention & control Lipid Peroxidation* Lipids / chemistry* Liver Neoplasms / chemically induced Liver Neoplasms / chemistry Liver Neoplasms / drug therapy Liver Neoplasms / metabolism Molecular Structure Oxidative Stress / drug effects Rats Spectrometry, Fluorescence
IF 12.587
Times Cited 18
Human and Animal Cells Hepa 1-6(RCB1638) Hep G2(RCB1886)