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A novel near-infrared fluorescent probe for intracellular detection of cysteine

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Abstract

Cysteine (Cys) takes part in redox balance in cells as an antioxidant, and imbalance of Cys content in the body can cause a variety of diseases. It is very important to develop a new fluorescent chemosensor to specifically detect Cys intracellular. In this work, a novel NIR fluorescent probe was constructed based on 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indol-3-ium iodide and 5-(4-hydroxyphenyl)furan-2-carbaldehyde. The probe could selectively detect Cys in the presence of homocysteine (Hcy), glutathione (GSH), and other interferences. It also had a number of advantages, including nucleolus-targeting ability, long fluorescence emission wavelength (685 nm), low detection limit (56 nM), and large Stokes shift (172 nm). The probe was employed to enable visualization of Cys in HepG2 cells, and due to its good response in viscous environment, the probe could also locate nucleoli intracellular.

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References

  1. Reddie KG, Carroll KS. Expanding the functional diversity of proteins through cysteine oxidation. Curr Opin Chem Biol. 2008;12:746–54.

    Article  CAS  Google Scholar 

  2. Zhang Y, Wang X, Bai X, Li P, Su D, Zhang W, et al. Highly specific Cys fluorescence probe for living mouse brain imaging via evading reaction with other biothiols. Anal Chem. 2019;91:8591–4.

    Article  CAS  Google Scholar 

  3. Perez-de-Arce K, Foncea R, Leighton F. Reactive oxygen species mediates homocysteine-induced mitochondrial biogenesis in human endothelial cells: modulation by antioxidants. Biochem Bioph Res Co. 2005;338:1103–9.

    Article  CAS  Google Scholar 

  4. Weerapana E, Wang C, Simon GM, Richter F, Khare S, Dillon MBD, et al. Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature. 2010;468:790–79.

    Article  CAS  Google Scholar 

  5. Paul BD, Sbodio JI, Xu R, Vandiver MS, Cha JY, Snowman AM, et al. Cystathionine gamma-lyase deficiency mediates neurodegeneration in Huntington’s disease. Nature. 2014;509:96–7.

    Article  CAS  Google Scholar 

  6. Lin J, Lee IM, Song Y, Cook NR, Selhub J, Manson JE, et al. Plasma homocysteine and cysteine and risk of breast cancer in women. Cancer Res. 2010;70:2397–405.

    Article  CAS  Google Scholar 

  7. Tobin DJ. Human hair pigmentation--biological aspects. Int J Cosmet Sci. 2008;30:233–57.

    Article  CAS  Google Scholar 

  8. Fox JH, Barber DS, Singh B, Zucker B, Swindell MK, Norflus F, et al. Cystamine increases L-cysteine levels in Huntington’s disease transgenic mouse brain and in a PC12 model of polyglutamine aggregation. J Neurochem. 2004;91:413–22.

    Article  CAS  Google Scholar 

  9. Amarnath K, Amarnath V, Amarnath K, Valentine HL, Valentine WM. A specific HPLC-UV method for the determination of cysteine and related aminothiols in biological samples. Talanta. 2003;60:1229–38.

    Article  CAS  Google Scholar 

  10. Zhou M, Ding J, Guo LP, Shang QK. Electrochemical behavior of L-cysteine and its detection at ordered mesoporous carbon-modified glassy carbon electrode. Anal Chem. 2007;79:5328–35.

    Article  CAS  Google Scholar 

  11. Jiang W-L, Li Y, Wang W-X, Zhao Y-T, Fei J, Li C-Y. A hepatocyte-targeting near-infrared ratiometric fluorescent probe for monitoring peroxynitrite during drug-induced hepatotoxicity and its remediation. Chem Commun. 2019;55:14307–10.

    Article  CAS  Google Scholar 

  12. You J, Zhang H, Zhang H, Yu A, Xiao T, Wang Y, et al. Determination of triazines in infant nutrient cereal-based foods by pressurized microwave-assisted extraction coupled with high-performance liquid chromatography–mass spectrometry. J Chromatogr B. 2007;856:278–84.

    Article  CAS  Google Scholar 

  13. Zhang M, Wang L, Zhao Y, Wang F, Wu J, Liang G. Using bioluminescence turn-on to detect cysteine in vitro and in vivo. Anal Chem. 2018;90:4951–4.

    Article  CAS  Google Scholar 

  14. Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Robert H. Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem. 1993;39:1764–79.

    Article  CAS  Google Scholar 

  15. Tian M, Guo F, Sun Y, Zhang W, Miao F, Liu Y, et al. A fluorescent probe for intracellular cysteine overcoming the interference by glutathione. Org Biomol Chem. 2014;12:6128–33.

    Article  CAS  Google Scholar 

  16. Yin J, Kwon Y, Kim D, Lee D, Kim G, Hu Y, et al. Cyanine-based fluorescent probe for highly selective detection of glutathione in cell cultures and live mouse tissues. J Am Chem Soc. 2014;136:5351–8.

    Article  CAS  Google Scholar 

  17. Wang X-d, Fan L, Ge J-y, Li F, Zhang C-h, Wang J-j, et al. A lysosome-targetable fluorescent probe for real-time imaging cysteine under oxidative stress in living cells. Spectrochim Acta A. 2019;221:117175.

    Article  CAS  Google Scholar 

  18. Jiao S, He X, Xu L, Ma P, Liu C, Huang Y, et al. A red-emitting fluorescence turn-on probe for the discrimination of cysteine from biothiols and its bioimaging applications in living cells. Sensor Actuat B-Chem. 2019;290:47–52.

    Article  CAS  Google Scholar 

  19. Chao J, Li M, Liu Y, Zhang Y, Huo F, Yin C. Fluorescence detection and imaging in zebrafish and Arabidopsis thaliana based on Cys/Hcy breaking space effect. Sensor Actuat B-Chem. 2019;298:126844.

    Article  CAS  Google Scholar 

  20. Zhao CC, Li X, Wang FY. Target-triggered NIR emission with a large Stokes shift for the detection and imaging of cysteine in living cells. Chem-Asian J. 2014;9:1777–81.

    Article  CAS  Google Scholar 

  21. Xu Y, Ren F, Liu H, Zhang H, Han Y, Liu Z, et al. Cholesterol-modified black phosphorus nanospheres for the first NIR-II fluorescence bioimaging. ACS Appl Mater Interfaces. 2019;11:21399–407.

    Article  CAS  Google Scholar 

  22. Feng Z, Yu X, Jiang M, Zhu L, Zhang Y, Yang W, et al. Excretable IR-820 for in vivo NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor. Theranostics. 2019;9:5706–19.

    Article  CAS  Google Scholar 

  23. Sheng Z, Guo B, Hu D, Xu S, Wu W, Liew WH, et al. Bright aggregation-induced-emission dots for targeted synergetic NIR-II fluorescence and NIR-I photoacoustic imaging of orthotopic brain tumors. Adv Mater. 2018;30:1800766.

    Article  Google Scholar 

  24. Zhang J, Jiang XD, Shao XM, Zhao JL, Su YJ, Xi DM, et al. A turn-on NIR fluorescent probe for the detection of homocysteine over cysteine. RSC Adv. 2014;4:54080–3.

    Article  CAS  Google Scholar 

  25. Zhang X, Chen X, Zhang Y, Liu K, Shen H, Zheng E, et al. A near-infrared fluorescent probe for the ratiometric detection and living cell imaging of beta-galactosidase. Anal Bioanal Chem. 2019;411:7957–66.

    Article  CAS  Google Scholar 

  26. Liu L, Zhang H, Wang Z, Song D. Peptide-functionalized upconversion nanoparticles-based FRET sensing platform for Caspase-9 activity detection in vitro and in vivo. Biosens Bioelectron. 2019;141:111403.

    Article  CAS  Google Scholar 

  27. Huo F, Kang J, Yin C, Zhang Y, Chao J. A turn-on green fluorescent thiol probe based on the 1,2-addition reaction and its application for bioimaging. Sensor Actuat B-Chem. 2015;207:139–43.

    Article  CAS  Google Scholar 

  28. Liu XJ, Yang DL, Chen WQ, Yang L, Qi FP, Song XZ. A red-emitting fluorescent probe for specific detection of cysteine over homocysteine and glutathione with a large Stokes shift. Sensor Actuat B-Chem. 2016;234:27–33.

    Article  CAS  Google Scholar 

  29. Li HD, Jin LY, Kan YH, Yin BZ. A visual and “turn-on” fluorescent probe for rapid detection of cysteine over homocysteine and glutathione. Sensor Actuat B-Chem. 2014;196:546–54.

    Article  CAS  Google Scholar 

  30. Li X, Ma H, Qian J, Cao T, Teng Z, Iqbal K, et al. Ratiometric fluorescent probe based on ESIPT for the highly selective detection of cysteine in living cells. Talanta. 2019;194:717–22.

    Article  CAS  Google Scholar 

  31. Huang Y, Qi Y, Zhan C, Zeng F, Wu S. Diagnosing drug-induced liver injury by multispectral optoacoustic tomography and fluorescence imaging using a leucine-aminopeptidase-activated probe. Anal Chem. 2019;91:8085–92.

    Article  CAS  Google Scholar 

  32. Hosoya T, Aoyama H, Ikemoto T, Kihara Y, Hiramatsu T, Endo M, et al. Dantrolene analogues revisited: general synthesis and specific functions capable of discriminating two kinds of Ca2+ release from sarcoplasmic reticulum of mouse skeletal muscle. Bioorg Med Chem. 2003;11:663–73.

    Article  CAS  Google Scholar 

  33. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al. Gaussian 16, Revision A.03. Wallingford: Gaussian Inc; 2016.

    Google Scholar 

  34. Lu T, Chen F. Multiwfn: a multifunctional wavefunction analyzer. J Comput Chem. 2012;33:580–92.

    Article  Google Scholar 

  35. Li Y, Chu T-S. DFT/TDDFT study on the sensing mechanism of a fluorescent probe for hydrogen sulfide: excited state intramolecular proton transfer coupled twisted intramolecular charge transfer. J Phys Chem A. 2017;121:5245–56.

    Article  CAS  Google Scholar 

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Funding

This work was supported by the Science and Technology Developing Foundation of Jilin Province of China (Nos. 20200602047ZP, 20200404173YY, and 20180201050YY).

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Correspondence to Pinyi Ma or Ying Sun.

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Zhao, L., He, X., Huang, Y. et al. A novel near-infrared fluorescent probe for intracellular detection of cysteine. Anal Bioanal Chem 412, 7211–7217 (2020). https://doi.org/10.1007/s00216-020-02853-9

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