Bioluminescent Sensor Reveals that Carboxylesterase 1A is a Novel Endoplasmic Reticulum-Derived Serologic Indicator for Hepatocyte Injury

Discovery of novel liver injury indicators and development of practical assays to detect target indicator(s) would strongly facilitate the diagnosis of liver disorders. Herein, an alternative biomarker discovery strategy was applied to find suitable endoplasmic reticulum-resident protein(s) as serologic indicator(s) for hepatocyte injury via analysis of the human proteome database among plasma and various organs. Both database searching and preliminary experiments suggested that human carboxylesterase 1A (CES1A), one of the most abundant and hepatic-restricted proteins, could serve as a good serologic indicator for hepatocyte injury. Then, a highly selective and practical bioluminescent sensor was developed for real-time sensing of CES1A in various biological systems including plasma. With the help of this bioluminescent sensor, the release of hepatic CES1A into the extracellular medium or the circulation system could be directly monitored. Further investigations demonstrated that serum activity levels of CES1A were elevated dramatically in mice with liver injury or patients with liver diseases. Collectively, this study provided solid evidence to support that CES1A was a novel serological indicator for hepatocyte injury. Furthermore, the strategy used in this study paved a new way for the rational discovery of practical indicators to monitor the dynamic progression of injury in a given tissue or organ.