Screening of Drug-Induced Steatosis and Phospholipidosis Using Lipid Droplet-Selective Two-Photon Probes

Lipid droplets (LDs) are organelles that play a major role in regulating the storage of neutral lipids. Dysregulation of LDs is associated with metabolic disorders, such as fatty liver diseases, obesity, diabetes, and atherosclerosis. We have developed LD-selective small-molecule fluorescence probes...

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Veröffentlicht in:Analytical chemistry (Washington) 2020-08, Vol.92 (16), p.11223-11231
Hauptverfasser: Cho, Myoung Ki, Seo, Min Ji, Juvekar, Vinayak, Jo, Jae Hyung, Kim, Wontae, Choi, Kyeong Sook, Kim, Hwan Myung
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Sprache:eng
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Zusammenfassung:Lipid droplets (LDs) are organelles that play a major role in regulating the storage of neutral lipids. Dysregulation of LDs is associated with metabolic disorders, such as fatty liver diseases, obesity, diabetes, and atherosclerosis. We have developed LD-selective small-molecule fluorescence probes (probes 3 and 4) that are available for both one- and two-photon microscopy, employing live or fixed cells. We found that probes 3 and 4 sensitively detect the increased LDs in response to oleic acid or endoplasmic reticulum stress, both in cells and tissues of the liver. The narrow absorption and emission bands of probes 3 and 4 allow multicolor imaging for the study of the role of LDs in pathophysiology and LD-associated signaling by the coapplication of the probes for different organelles or antibodies against specific proteins. In addition, we show here, for the first time, that two-photon microscopy imaging using our LD-selective probes with LysoTracker provides a novel method for screening drugs to potentially induce steatosis and/or phospholipidosis.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.0c01728