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Screening of Drug-Induced Steatosis and Phospholipidosis Using Lipid Droplet-Selective Two-Photon Probes
  • Cho, Myoung Ki ;
  • Seo, Min Ji ;
  • Juvekar, Vinayak ;
  • Jo, Jae Hyung ;
  • Kim, Wontae ;
  • Choi, Kyeong Sook ;
  • Kim, Hwan Myung
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Publication Year
2020-08-18
Publisher
American Chemical Society
Citation
Analytical Chemistry, Vol.92, pp.11223-11231
Mesh Keyword
Absorption and emissionsAssociated signalingEndoplasmic reticulum stressFatty liver diseaseFluorescence probesMetabolic disordersMulticolor imagingTwo photon microscopy
All Science Classification Codes (ASJC)
Analytical Chemistry
Abstract
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- A nd 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.
Language
eng
URI
https://dspace.ajou.ac.kr/dev/handle/2018.oak/31491
DOI
https://doi.org/10.1021/acs.analchem.0c01728
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Type
Article
Funding
This study was supported by grants from the National Leading Research Lab Program of the National Research Foundation of Korea (NRF), funded by the Korean government (MSIP) (Grant NRF-2019R1A2B5B03100278), the Center for Convergence Research of Neurological Disorders (Grant NRF-2019R1A5A2026045), and the Ajou University Research Fund. K.S.C. acknowledges a grant from the NRF (Grant NRF-2019R1F1A1062842).
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Kim, Hwan Myung김환명
Department of Chemistry
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