抄録
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.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 608-613 |
| ページ数 | 6 |
| ジャーナル | Nature Chemical Biology |
| 巻 | 12 |
| 発行部数 | 8 |
| DOI | |
| 出版物ステータス | 出版済み - 8 1 2016 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology
これを引用
Fluorescence probes to detect lipid-derived radicals. / Yamada, Ken-Ichi; Mito, Fumiya; Matsuoka, Yuta; Ide, Satsuki; Shikimachi, Kazushige; Fujiki, Ayano; Kusakabe, Daiki; Ishida, Yuma; Enoki, Masataka; Tada, Arisa; Ariyoshi, Miyuki; Yamasaki, Toshihide; Yamato, Mayumi.
：: Nature Chemical Biology, 巻 12, 番号 8, 01.08.2016, p. 608-613.研究成果: ジャーナルへの寄稿 › 記事
}
TY - JOUR
T1 - Fluorescence probes to detect lipid-derived radicals
AU - Yamada, Ken-Ichi
AU - Mito, Fumiya
AU - Matsuoka, Yuta
AU - Ide, Satsuki
AU - Shikimachi, Kazushige
AU - Fujiki, Ayano
AU - Kusakabe, Daiki
AU - Ishida, Yuma
AU - Enoki, Masataka
AU - Tada, Arisa
AU - Ariyoshi, Miyuki
AU - Yamasaki, Toshihide
AU - Yamato, Mayumi
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nchembio.2105
DO - 10.1038/nchembio.2105
M3 - Article
VL - 12
SP - 608
EP - 613
JO - Nature Chemical Biology
JF - Nature Chemical Biology
SN - 1552-4450
IS - 8
ER -