Reference - Detail
|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|
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.
|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|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY|
|Human and Animal Cells||Hepa 1-6(RCB1638) Hep G2(RCB1886)|