Screening of Drug-Induced Steatosis and Phospholipidosis Using Lipid Droplet-Selective Two-Photon Probes.
Myoung Ki ChoMin Ji SeoVinayak JuvekarJae Hyung JoWontae KimKyeong Sook ChoiHwan Myung KimPublished in: Analytical chemistry (2020)
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.
Keyphrases
- small molecule
- living cells
- single molecule
- induced apoptosis
- fluorescence imaging
- endoplasmic reticulum stress
- drug induced
- high resolution
- fluorescent probe
- insulin resistance
- protein protein
- liver injury
- type diabetes
- cardiovascular disease
- cell cycle arrest
- high throughput
- fatty acid
- photodynamic therapy
- high fat diet
- nucleic acid
- metabolic syndrome
- adipose tissue
- body mass index
- optical coherence tomography
- gene expression
- weight gain
- high speed
- cell proliferation
- flow cytometry
- glycemic control