High Turnover Rates for Hydrogen Sulfide Allow for Rapid Regulation of Its Tissue Concentrations

Abstract

Aims: Hydrogen sulfide (H 2 S) is a signaling molecule, which influences many physiological processes. While H 2 S is produced and degraded in many cell types, the kinetics of its turnover in different tissues has not been reported. In this study, we have assessed the rates of H 2 S production in murine liver, kidney, and brain homogenates at pH 7.4, 37°C, and at physiologically relevant cysteine concentrations. We have also studied the kinetics of H 2 S clearance by liver, kidney, and brain homogenates under aerobic and anaerobic conditions. Results: We find that the rate of H 2 S production by these tissue homogenates is considerably higher than background rates observed in the absence of exogenous substrates. An exponential decay of H 2 S with time is observed and, as expected, is significantly faster under aerobic conditions. The half-life for H 2 S under aerobic conditions is 2.0, 2.8, and 10.0 min with liver, kidney, and brain homogenate, respectively. Western-blot analysis of the sulfur dioxygenase, ETHE1, involved in H 2 S catabolism, demonstrates higher steady-state protein levels in liver and kidney versus brain. Innovation: By combining experimental and simulation approaches, we demonstrate high rates of tissue H 2 S turnover and provide estimates of steady-state H 2 S levels. Conclusion: Our study reveals that tissues maintain a high metabolic flux of sulfur through H 2 S, providing a rationale for how H 2 S levels can be rapidly regulated. Antioxid. Redox Signal. 17, 22-31.

Key bioactive reaction products of the NO/H2S interaction are S/N-hybrid species, polysulfides, and nitroxyl

“…S1 A and B), showing that endogenous NO production modulates sulfide bioactivity and attesting to the reciprocal nature of interaction of these signaling molecules. In subsequent experiments, NaHS was administered by continuous infusion (2.8 μmol/kg per minute in PBS, pH 7.4) to counter the rapid rate of sulfide elimination (33), and blood was collected repeatedly for measurement of circulating NO biomarkers ( Fig. 1 and SI Appendix, Fig.…”

“…The results of this study suggest that HS n − are also intermediates in SSNO − formation, possibly through homolytic cleavage to radical species and subsequent reaction with NO. Thus, in addition to their enzymatic formation (33) and as a consequence of sulfide oxidation (50), reaction of sulfide with NO or nitrosothiols may provide another pathway to their production in cells and tissues.…”

S-Glutathionylation Enhances Human Cystathionine β-Synthase Activity Under Oxidative Stress Conditions

“…Control reactions in which buffer replaced the cell lysate were prepared in parallel. Aliquots of 0.1-0.3 ml from the gas phase of the reaction syringes were collected using gas-tight syringes inserted through a septum attached to the stopcock, and injected in an HP 6890 gas chromatograph (Hewlett Packard) that was equipped with a DB-1 column (30 m · 0.53 mm · 1.0 lm) as previously described (53). Helium was used as the carrier gas at a flow rate of 1 ml/min, and a temperature gradient ranging from 30°C to 110°C over a 20 min period was used.…”

Highly sensitive sulphide mapping in live cells by kinetic spectral analysis of single Au-Ag core-shell nanoparticles

“…Although most publications suggest that the average endogenous H 2 S level is in the mM range, much lower sulphide concentrations have been reported 29 . More importantly, the anabolism and catabolism of cellular sulphide are known to be rapid, which means that the sulphide concentration could fluctuate continuously from as high as submM during its explosive production to as low as a few nM after its rapid consumption 30 . However, almost all existing H 2 Ssensing methods are based on some irreversible stoichiometric reaction between the probe and sulphide species [23][24][25][26][27][28] and cannot be utilized to monitor the dynamics of sulphide generation and elimination inside cells, especially at the single-molecule level.…”