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一种新型的线粒体靶向双光子荧光探针,用于动态可逆地检测过氧亚硝酸盐和谷胱甘肽之间的氧化还原循环。

A novel mitochondria-targeted two-photon fluorescent probe for dynamic and reversible detection of the redox cycles between peroxynitrite and glutathione.

作者信息

Sun Chunlong, Du Wen, Wang Peng, Wu Yang, Wang Baoqin, Wang Jun, Xie Wenjun

机构信息

School of Biotechnology, Key Laboratory of Instrumental Analysis of Binzhou City, Shandong Provincial Key Laboratory of Eco-environmental Science for Yellow River Delta, Binzhou University, Binzhou 256603, China.

Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China.

出版信息

Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):518-525. doi: 10.1016/j.bbrc.2017.10.123. Epub 2017 Oct 24.

DOI:10.1016/j.bbrc.2017.10.123
PMID:29079191
Abstract

Redox homeostasis is important for maintenance of normal physiological functions within cells. Redox state of cells is primarily a consequence of precise balance between levels of reducing equivalents and reactive oxygen species. Redox homeostasis between peroxynitrite (ONOO) and glutathione (GSH) is closely associated with physiological and pathological processes, such as prolonged relaxation in vascular tissues and smooth muscle preparations, attenuation of hepatic necrosis, and activation of matrix metalloproteinase-2. We report a two-photon fluorescent probe (TP-Se) based on water-soluble carbazole-based compound, which integrates with organic selenium, to monitor changes in ONOO/GSH levels in cells. This probe can reversibly respond to ONOO and GSH and exhibits high selectivity, sensitivity, and mitochondrial targeting. The probe was successfully applied to visualize changes in redox cycles during ONOO outbreak and antioxidant GSH repair in cells. The probe will lead to significant development on redox events involved in cellular redox regulation.

摘要

氧化还原稳态对于维持细胞内正常生理功能至关重要。细胞的氧化还原状态主要是还原当量水平与活性氧物种之间精确平衡的结果。过氧亚硝酸根(ONOO)和谷胱甘肽(GSH)之间的氧化还原稳态与生理和病理过程密切相关,如血管组织和平滑肌制剂中的长时间舒张、肝坏死的减轻以及基质金属蛋白酶-2的激活。我们报道了一种基于水溶性咔唑类化合物并与有机硒结合的双光子荧光探针(TP-Se),用于监测细胞中ONOO/GSH水平的变化。该探针可对ONOO和GSH做出可逆响应,具有高选择性、高灵敏度和线粒体靶向性。该探针已成功应用于可视化细胞中ONOO爆发和抗氧化剂GSH修复过程中的氧化还原循环变化。该探针将推动细胞氧化还原调节中涉及的氧化还原事件的重大发展。

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