Novel bisbenzimide-nitroxides for nuclear redox imaging in living cells.
Nuclear oxidative stress damages genomic DNA and may lead to cell death, leading to aging and aging-related disorders. Though it is important to measure the nuclear oxidative stress separately, there are still little examples that applicable to living cells. We have designed and synthesized three bisbenzimide-nitroxides as probes to selectively visualize nuclear redox changes in terms of fluorescence. Compound 3, containing two radical moieties, showed the largest reduction-induced fluorescence change, with good localization in nuclei. RAW264.7 murine macrophage cells were loaded with compound 3 and then treated with 100μM hydrogen peroxide for 5min to show the fluorescence increase. This fluorescence increase was inhibited by pretreatment of 1mM ascorbic acid. These results show that compound 3 was suitable for nuclear-specific redox imaging in murine macrophages.
Graduate School of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori 3-1, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Mamiko
M
Ikeda
Hidehiko
H
Nakagawa
Takayoshi
T
Suzuki
Naoki
N
Miyata
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D006690:Bisbenzimidazole / Q000032:analysis*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005456:Fluorescent Dyes / Q000032:analysis*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009589:Nitrogen Oxides / Q000032:analysis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013050:Spectrometry, Fluorescence
D005456:Fluorescent Dyes; D009589:Nitrogen Oxides; D004247:DNA; D006861:Hydrogen Peroxide; D006690:Bisbenzimidazole; D001205:Ascorbic Acid