A fluorescent probe for bioimaging of Hexosaminidases activity and exploration of drug-induced kidney injury in living cell.

ABSTRACT

Hexosaminidases (Hexs) as an exoglycosidase participates in the catalytic hydrolysis of non-reducing end of glycoconjugates in the biological system. The fluctuation of Hexs level could cause many hereditary neurodegenerative diseases such as Tay-Sachs and Sandhoff. The Hexs activity is significantly up-regulated in colorectal cancer and kidney injury tissue so that it is particularly important to construct a fluorescent probe with significant signal change to understand its physiological role. In this work, DyOH was selected as fluorophore scaffolds to synthesize probe Hex-1 for detection of Hexs with good water solubility, high specificity, large stokes shift and quick response. Hex-1 can sensitively detect Hexs with the low detection limit (0.025 mU mL-1) in vitro by "naked eye" due to superior spectral properties of DyOH. Furthermore, Hex-1 was not only employed for imaging Hexs in living cells with low toxicity, but also successfully applied to evaluate the fluctuation of Hexs activity during drug induced kindey injury in living HK-2 cells. These results indicated that Hex-1 could be used as a potential image tool to further explore the pathogenesis of kidney disease and cancer.