Novel bisbenzimide-nitroxides for nuclear redox imaging in living cells

Novel bisbenzimide-nitroxides for nuclear redox imaging in living cells
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DOI:
10.1016/j.bmcl.2012.01.042
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发表时间:
2012-03-01
影响因子:
2.7
通讯作者:
Miyata, Naoki
Miyata, Naoki
中科院分区:
医学4区
文献类型:
--
作者:
Ikeda, Mamiko;Nakagawa, Hidehiko;Miyata, Naoki

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核氧化应激损伤基因组DNA,可能导致细胞死亡,导致衰老和衰老相关疾病。虽然单独测量核氧化应激很重要,但适用于活细胞的例子仍然很少。我们设计并合成了三种双苯甲酰亚胺-氮氧化物作为探针,以荧光的形式选择性地观察核氧化还原的变化。化合物3含有两个自由基基团,还原诱导的荧光变化最大,且定位于核内。用化合物3负载RAW264.7小鼠巨噬细胞,再用100 mU M过氧化氢处理5min,使其荧光增强。这种荧光增强可被1 mM抗坏血酸预处理所抑制。这些结果表明,化合物3适合于小鼠巨噬细胞核特异性氧化还原成像。(C)2012爱思唯尔有限公司。保留所有权利。
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 100 mu M hydrogen peroxide for 5 min to show the fluorescence increase. This fluorescence increase was inhibited by pretreatment of 1 mM ascorbic acid. These results show that compound 3 was suitable for nuclear-specific redox imaging in murine macrophages. (c) 2012 Elsevier Ltd. All rights reserved.