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

Abstract

Abstract Aims: Hydrogen sulfide (H2S) is a signaling molecule, which influences many physiological processes. While H2S 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 H2S 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 H2S clearance by liver, kidney, and brain homogenates under aerobic and anaerobic conditions. Results: We find that the rate of H2S production by these tissue homogenates is considerably higher than background rates observed in the absence of exogenous substrates. An exponential decay of H2S with time is observed and, as expected, is significantly faster under aerobic conditions. The half-life for H2S 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 H2S 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 H2S turnover and provide estimates of steady-state H2S levels. Conclusion: Our study reveals that tissues maintain a high metabolic flux of sulfur through H2S, providing a rationale for how H2S levels can be rapidly regulated. Antioxid. Redox Signal. 17, 22?31.