title: A new endoplasmic reticulum-targeted two-photon fluorescent probe for imaging of superoxide anion in diabetic mice.
abstract: Excessive or unfolded proteins accumulation in endoplasmic reticulum (ER) will cause ER stress, which has evolved to involve in various metabolic diseases. In particular, ER stress plays an important role in the pathogenesis of diabetes. Both ER stress and course of diabetes accompany oxidative stress and production of reactive oxygen species (ROS), among which superoxide anion (O2•-) is the first produced ROS and has been recognized as cell signaling mediator involved in the physiological and pathological process of diabetes. Hence, the development of effective monitoring methods of O2•-in live cells and in vivo is of great importance for ascertaining the onset and progress of related diseases. Herein, a new endoplasmic reticulum-targeted two-photon fluorescent probe termed ER-BZT is designed and synthesized for imaging of O2•-. The probe ER-BZT shows high sensitivity, selectivity, stability, and low cytotoxicity. Based on these superior properties, the rise of O2•-levels in endoplasmic reticulum induced with different stimuli is visualized by one- and two-photon fluorescence imaging. Most importantly, by utilizing ER-BZT, the two-photon fluorescence imaging results demonstrate that the endogenous O2•-concentration in abdominal or hepatic tissue of diabetic mice is higher than that in normal mice. Meanwhile, after treated with metformin, a broad-spectrum antidiabetic drug, the diabetic mice exhibit depressed O2•-level. The proposed two-photon probe, ER-BZT might serve as perfect tool to image the O2•-fluctuations and study the relevance between O2•-and various diseases in live cells and in vivo.
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Institute of Biomedical Sciences, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, PR China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Xiao
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Institute of Biomedical Sciences, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Institute of Biomedical Sciences, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, PR China.
authors.forename: Chuanchen
authors.initials: C
authors.lastname: Wu
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Institute of Biomedical Sciences, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, PR China.
authors.forename: Yaohuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Institute of Biomedical Sciences, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Institute of Biomedical Sciences, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, PR China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Guo
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Institute of Biomedical Sciences, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, PR China. Electronic address: tangb@sdnu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000379:methods; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology*; D059865:Endoplasmic Reticulum Stress; D005456:Fluorescent Dyes / Q000737:chemistry*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D061848:Optical Imaging / Q000379:methods*; D018384:Oxidative Stress; D000067996:RAW 264.7 Cells; D013481:Superoxides / Q000032:analysis* / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D013481:Superoxides
keywords: Diabetes; Endoplasmic reticulum; Fluorescent probe; Imaging; Superoxide anion; Two-photon