A Panel of Protein Kinase Chemosensors Distinguishes Different Types of Fatty Liver Disease

Authors

Jon R. Beck, University of Nebraska-Lincoln
Fatima Cabral, University of Nebraska - LincolnFollow
Karuna Rasineni, University of Nebraska Medical Center & Nebraska-Western Iowa Health Care System
Carol A. Casey, University of Nebraska Medical Center & Nebraska-Western Iowa Health Care System & University of Nebraska - LincolnFollow
Edward N. Harris, University of Nebraska - Lincoln & University of Nebraska Medical CenterFollow
Cliff I. Stains, University of Nebraska - Lincoln & University of Nebraska Medical Center & University of VirginiaFollow

ORCID IDs

0000-0001-7045-1040

0000-0002-3165-4539

Date of this Version

8-21-2019

Citation

2019 American Chemical Society

Comments

DOI: 10.1021/acs.biochem.9b00547 Biochemistry 2019, 58, 3911−3917

Abstract

The worldwide incidence of fatty liver disease continues to rise, which may account for concurrent increases in the frequencies of more aggressive liver ailments. Given the existence of histologically identical fatty liver disease subtypes, there is a critical need for the identification of methods that can classify disease and potentially predict progression. Herein, we show that a panel of protein kinase chemosensors can distinguish fatty liver disease subtypes. These direct activity measurements highlight distinct differences between histologically identical fatty liver diseases arising from diets rich in fat versus alcohol and identify a previously unreported decrease in p38α activity associated with a high-fat diet. In addition, we have profiled kinase activities in both benign (dietinduced) and progressive (STAM) disease models. These experiments provide temporal insights into kinase activity during disease development and progression. Altogether, this work provides the basis for the future development of clinical diagnostics and potential treatment strategies.