Prodigiosin, anion transporter, fluorescence imaging, apoptosis inducing, lysosome disrupting, NIR-AZA fluorophore.
Science Foundation Ireland grant number 11/PI/ 1071(T)
The unraveling of the cellular effects of anion transporters is key to their potential development as apoptosis-inducing or autophagy-disrupting therapeutics. Here, we conducted a systematic study of the cellular responses to the anion transporter prodigiosin by using a pH on/off responsive near-infrared (NIR)-fluorescent probe in HeLa and LAMP1-GFP-transfected HeLa cell lines. The sequence of localized and global cellular acidity changes and the resulting outcomes induced by the anion transporter were visualized with high temporal and spatial resolution. The results show that prodigiosin causes the pH within the lysosomal lumen to rise, after which a non-organelle-specific increase in acidity of the cytosol takes place, which prompts cells to undergo apoptosis. This was confirmed by the quantification of NIR-emissive lysosomes, the intra-cellular fluorescence intensity, and fluorescence volume over time. This NIR probe overcame the limitations of acridine orange, which to date have severely restricted researchers in this field.
Chemistry | Medicinal-Pharmaceutical Chemistry | Medicine and Health Sciences
Cheung S, Wu D, Daly HC, Busschaert N, Morgunova M, Simpson JC, Scholz D, Gale PA, O’Shea DF. Real-Time Recording of the Cellular Effects of the Anion Transporter Prodigiosin. Chem. 2018;4(4):879-895.
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Available for download on Friday, April 12, 2019