Hydrogen selenide,a vital metabolite of sodium selenite,uncouples the sulfilimine bond and promotes the reversal of liver fibrosis

Sodium selenite has alleviating effects on liver fibrosis;however,its therapeutic molecular mechanism remains unclear.Herein,hydrogen selenide,a major metabolite of Na_(2)SeO_(3),was tested to uncouple the sulfilimine bond in collagen IV,the biomarker of liver fibrosis.A mouse model of liver fibrosis was constructed via a CCl_(4)-induced method,followed by the administration of 0.2 mg kg−1 Na_(2)SeO_(3)via gavage three times per week for 4 weeks.Changes in H2Se,NADPH,and H_(2)O_(2)levels were monitored in real time by using NIR-H2Se,DCI-MQ-NADPH,and H_(2)O_(2)probes in vivo,respectively.H_(2)Se continuously accumulated in the liver throughout the Na_(2)SeO_(3)treatment period,but the levels of NADPH and H_(2)O_(2)decreased.The expression of collagen IV was analyzed through Western blot and liquid chromatography-mass spectrometry.Results confirmed that the sulfilimine bond of collagen IV in the fibrotic mouse livers could be broken by H2Se with the Na_(2)SeO_(3)treatment.Therefore,the therapeutic effect of Na_(2)SeO_(3)on liver fibrosis could be mainly attributed to H_(2)Se that uncoupled the sulfilimine bond to induce collagen IV degradation.This study provided a reasonable explanation for the molecular mechanism of the in vivo function of Na_(2)SeO_(3)and the prevention of liver fibrosis by administering inorganic selenium.

Visualization of the process:selenocysteine activates GPX4 in ferroptosis based on a nano-fluorescent probe

Developing accurate methods for visualizing the expressions of proteins during the life process is a hotspot in the biochemical research field.Glutathione peroxidase 4(GPX4),one type of selenoproteins,was previously identified as a significant ferroptosis-regulated protein.Therefore,a novel approach was established to visualize the activation process of selenocysteine(Sec)toward GPX4 via an Au–Se bonded fluorescent nanoprobe and assisted by western blot analysis.The Au–Se nanoprobe was constructed by selenol-modified peptides for monitoring the concentration changes of Sec.The fluorescence intensity of Sec in confocal fluorescence imaging positively correlates with GPX4's activation level,proved by western blot analysis in living cells.This study provides an intuitional and visual strategy for predicting the functional expression of GPX4 during the ferroptosis process and offers new directions for the future investigation of proteins'functional expressions.