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Dynamic Imaging of Adaptive Stress Response Pathway Activation for Prediction of Drug Induced Liver Injury by Steven Wink; Steven W. Hiemstra; Suzanne Huppelschoten; Janna E. Klip; Bob van de Water is a Environmental Science article available to read on EtoBox.

What is Dynamic Imaging of Adaptive Stress Response Pathway Activation for Prediction of Drug Induced Liver Injury about?

Drug-induced liver injury remains a concern during drug treatment and development. There is an urgent need for improved mechanistic understanding and prediction of DILI liabilities using in vitro approaches. We have established and characterized a panel of liver cell models containing mechanism-based fluorescent protein toxicity pathway reporters to quantitatively assess the dynamics of cellular stress response pathway activation at the single cell level using automated live cell imaging. We have systematically evaluated the application of four key adaptive stress pathway reporters for the prediction of DILI liability: SRXN1-GFP (oxidative stress), CHOP-GFP (ER stress/UPR response), p21 (p53-mediated DNA damage-related response) and ICAM1 (NF-κB-mediated inflammatory signaling). 118 FDA-labeled drugs in five human exposure relevant concentrations were evaluated for reporter activation using live cell confocal imaging. Quantitative data analysis revealed activation of single or multiple reporters by most drugs in a concentration and time dependent manner. Hierarchical clustering of time course dynamics and refined single cell analysis allowed the allusion of key events in DILI liabi

Who reads Dynamic Imaging of Adaptive Stress Response Pathway Activation for Prediction of Drug Induced Liver Injury?

Author

Steven Wink; Steven W. Hiemstra; Suzanne Huppelschoten; Janna E. Klip; Bob van de Water

Publisher

Springer Science and Business Media LLC

Published

2018

Language

EN

Field

Environmental Science (Life Sciences)