A new class of fast-response and highly selective fluorescent probes for visualizing peroxynitrite in live cells, subcellular organelles, and kidney tissue of diabetic rats.
Peroxynitrite (ONOO(-)) is an extremely powerful oxidant in biological systems, and can react with a wide variety of molecular targets including proteins, lipids, and nucleic acids, eventually resulting in a series of disease states such as diabetes, Alzheimer's disease, cancer, arthritis, autoimmune, and other disorders. In this work, we present a new class of ONOO(-) fluorescent probes by exploiting the ONOO(-)-triggered N-oxidation and N-nitrosation reactions of aromatic tertiary amine for the first time. The as-obtained fluorescent probe A2 could detect ONOO(-) with quite fast fluorescence off-on response (within seconds), ultrasensitivity (detection limit: <2 nM), and excellent selectivity over a series of biologically relevant reactive oxygen species as well as metal cations. With the probe, the endogenous ONOO(-) in activated RAW264.7 murine macrophage, EA.hy926 endothelial cells after oxygen glucose deprivation and reoxygenation (OGD/RO), and kidney tissue of diabetic rats has been successfully visualized. Based on the molecular platform of A2, we further develop its mitochondria- and lysosome-targetable fluorescent probes Mito-A2 and Lyso-A2 by installing the corresponding targeting groups to alkoxy unit of A2, and confirm their abilities to image ONOO(-) in mitochondria and lysosomes, respectively, by co-localization assays. It is greatly expected that these probes can serve as useful imaging tools for clarifying the distribution and pathophysiological functions of ONOO(-) in cells, subcellular organelles, and animal tissues.
School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China.
Junfeng
J
Miao
School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China.
Yingying
Y
Huo
School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China.
Qian
Q
Liu
School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China.
Zhe
Z
Li
School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China.
Heping
H
Shi
Institute of Biotechnology, Shanxi University, Taiyuan 030006, China.
Yawei
Y
Shi
School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China. Electronic address: guow@sxu.edu.cn.
Wei
W
Guo
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry*; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013347:Subcellular Fractions / Q000378:metabolism*
D015415:Biomarkers; D005456:Fluorescent Dyes; D030421:Peroxynitrous Acid
Aromatic tertiary amine; Fluorescent probes; N-nitrosation; N-oxidation; Peroxynitrite