Endoplasmic Reticulum Targeting Ratiometric Fluorescent Probe for Carboxylesterase 2 Detection in Drug-Induced Acute Liver Injury

Xiangge Tian, Fei Yan, Jingyuan Zheng, Xiaolin Cui, Lei Feng, Sheng Li, Lingling Jin, Tony D. James, Xiaochi Ma

Research output: Contribution to journalArticle

Abstract

Carboxylesterase 2 (CES2), an endoplasmic reticulum (ER) located phase I enzyme, plays a vital role in the metabolism of various endogenous and exogenous substances, and is regarded as an important target for the design of prodrugs. Unfortunately, superior highly selective ER targeting fluorescent probes for monitoring of CES2 are not currently available. Herein, we report an ER targeting CES2 selective and sensitive ratiometric fluorescent probe ERNB based on the ER localizing group p-toluenesulfonamide. ERNB possessed high specificity, sensitivity, and exhibited excellent subcellular localization when compared to commercial ER tracker, and was used to image CES2 in the ER of living cells. Additionally, using ERNB we evaluated the CES2 regulation under d,l-dithiothreitol and tunicamycin-induced ER stress. Furthermore, we determined the down regulation of CES2 activity and expression in the acetaminophen-induced acute liver injury model. On the basis of these results, we conclude that ERNB is a promising tool for highlighting the role of CES2 in the ER and in exploring the role of CES2 in the development of diseases associated with ER stress.

Original languageEnglish
Pages (from-to)15840-15845
Number of pages6
JournalAnalytical Chemistry
Volume91
Issue number24
Early online date12 Nov 2019
DOIs
Publication statusPublished - 17 Dec 2019

ASJC Scopus subject areas

  • Analytical Chemistry

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