Fluorescent imaging to provide visualized evidences for mercury induced hypoxia stress

As one typical toxic and dangerous heavy metal, mercury brings incalculable hazards to the environment and human, the mechanism at the molecular level is unclear. There is no visualized evidence to support directly that mercury ions (Hg²⁺) exposure may induce secondary stress, which is associated with the risk of hypoxia microenvironment in biological systems. Hypoxia occurs in many physiological and pathophysiological processes in the living system, accompanying overexpression of various biomarkers, such as nitroreductase (NTR). Hence, we had successfully developed two NTR-selective fluorescent probes with excellent performance for evaluating the hypoxia degree in vivo and in vitro. We visualized and qualitatively monitored the fluctuations of the endogenous NTR levels in living cells and zebrafish. The imaging results exhibited that different doses of Hg²⁺ exposure elevated the NTR levels and the same trend in changes of NTR as extrinsic hypoxia exposure, suggesting that Hg²⁺ exposure induced microenvironmental changes resulting in the hypoxia stress. This is the first time to provide visual evidence to support that Hg²⁺ stress may involve in the intracellular hypoxia microenvironment through monitoring the dynamic of NTR levels in the living systems. Our results may provide a novel insight into the molecular mechanisms of typical heavy metal element induced toxicity.