Issue 16, 2019

Depletion of protein thiols and the accumulation of oxidized thioredoxin in Parkinsonism disclosed by a red-emitting and environment-sensitive probe

Abstract

Protein sulfhydryl groups play a vital role in maintaining cellular redox homeostasis and protein functions and have attracted increasing interests for the selective detection of protein thiols over low-molecular-weight thiols (LMWTs). Herein, we reported a red-emitting and environment-sensitive probe (FM-red) for detecting and labeling protein thiols. The probe contains a maleimide unit as a thiol receptor and an environment-sensitive fluorophore as a sensor. The emission signal of the probe was exclusively switched on by binding to protein sulfhydryl groups through the twisted intramolecular charge transfer mechanism, while negligible fluorescence was observed when FM-red reacted with LMWTs. Various experiments verified that FM-red possessed fast responsivity (∼10 min) and high selectivity to sense protein thiols over LMWTs with a red emission (∼655 nm). These favorable properties enable the probe to image protein sulfhydryl groups in live cells and in vivo. In addition, as FM-red has a relatively high molecular weight (MW 688), it is able to separate the labeled proteins from the unlabeled ones after FM-red derivatization via routine protein electrophoresis, which may be applied to determine the redox states of thioredoxin, a small redox protein ubiquitous in all cells. With the aid of the probe, we demonstrated a significant decrease in the protein thiols and the accumulation of oxidized thioredoxin in a cellular model of Parkinson's disease.

Graphical abstract: Depletion of protein thiols and the accumulation of oxidized thioredoxin in Parkinsonism disclosed by a red-emitting and environment-sensitive probe

Supplementary files

Article information

Article type
Paper
Submitted
24 11 2018
Accepted
11 3 2019
First published
13 3 2019

J. Mater. Chem. B, 2019,7, 2696-2702

Depletion of protein thiols and the accumulation of oxidized thioredoxin in Parkinsonism disclosed by a red-emitting and environment-sensitive probe

G. Hu, B. Zhang, P. Zhou, Y. Hou, H. Jia, Y. Liu, L. Gan, H. Zhang, Y. Mao and J. Fang, J. Mater. Chem. B, 2019, 7, 2696 DOI: 10.1039/C8TB03101K

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