Live-cell imaging approaches for the investigation of xenobiotic-induced oxidant stress

• Published in: Biochimica et biophysica acta Vol. 1860; no. 12; pp. 2802 - 2815
• Main Authors: Wages, Phillip A., Cheng, Wan-Yun, Gibbs-Flournoy, Eugene, Samet, James M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2016
• Subjects: Animals; biochemical compounds; Cell Survival - drug effects; Cells, Cultured; Fluorescence; fluorescent dyes; Fluorescent Dyes - chemistry; Gene Expression; Glutathione; Humans; image analysis; Live-cell imaging; Luminescent Proteins - analysis; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Molecular Imaging - methods; Molecular Probes - chemistry; Oxidant stress; oxidants; Oxidants - pharmacology; Oxidation-Reduction; Oxidative Stress; physiology; Reactive oxygen species; Reactive Oxygen Species - analysis; Reactive Oxygen Species - metabolism; Redox potential; Time-Lapse Imaging - methods; toxic substances; Toxicology; Xenobiotic; xenobiotics; Xenobiotics - pharmacology; Toxicology; Reactive oxygen species; Fluorescence; Live-cell imaging; Redox potential; Oxidant stress; Xenobiotic; Glutathione
• ISSN: 0304-4165; 0006-3002; 1872-8006; 1878-2434
• DOI: 10.1016/j.bbagen.2016.05.017

Oxidant stress is arguably a universal feature in toxicology. Research studies on the role of oxidant stress induced by xenobiotic exposures have typically relied on the identification of damaged biomolecules using a variety of conventional biochemical and molecular techniques. However, there is increasing evidence that low-level exposure to a variety of toxicants dysregulates cellular physiology by interfering with redox-dependent processes. The study of events involved in redox toxicology requires methodology capable of detecting transient modifications at relatively low signal strength. This article reviews the advantages of live-cell imaging for redox toxicology studies. Toxicological studies with xenobiotics of supra-physiological reactivity require careful consideration when using fluorogenic sensors in order to avoid potential artifacts and false negatives. Fortunately, experiments conducted for the purpose of validating the use of these sensors in toxicological applications often yield unexpected insights into the mechanisms through which xenobiotic exposure induces oxidant stress. Live-cell imaging using a new generation of small molecule and genetically encoded fluorophores with excellent sensitivity and specificity affords unprecedented spatiotemporal resolution that is optimal for redox toxicology studies. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. •Induction of oxidant stress is a common mechanistic feature in toxicology.•Spatiotemporal resolution of live-cell imaging can monitor transient oxidant events.•New generation of fluorogenic sensors offers superior sensitivity and specificity.•Small-molecule and genetically-encoded probes sense reactive species, redox status.•Toxicological application of oxidant stress imaging presents unique challenges.