Visualizing nitric oxide-dependent HIF-1 activity under hypoxia with a lipid droplet-targeting fluorescent probe

Evaluating the correlation between hypoxia inducible factor 1 (HIF-1) and nitric oxide (NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activity influenced by NO under hypoxia in hepatoma cells with dual-targeting for hepatocyte and lipid droplet (LD). The probe shows excellent selectivity to NO and high sensitivity with 600 0-fold fluorescence enhancement. Live cell imaging experiments revealed the probe's capability of imaging exogenous and endogenous NO with specific in LDs of HepG2 cells. For cells under hypoxia, HIF-1 induced LD level is observed to correlate with NO level. This work provides the in-situ visualization of NOdependent HIF-1 upregulation through LD accumulation. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

This study developed a fluorescent probe for monitoring the influence of NO on HIF-1 activity under hypoxia in hepatoma cells, with high selectivity and sensitivity. Live cell imaging experiments demonstrated the probe’s ability to image exogenous and endogenous NO in LDs, and revealed a correlation between HIF-1 induced LD level and NO level in hypoxic cells.