Dataset Information

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.

SUBMITTER: Vitvitsky V

PROVIDER: S-EPMC3342560 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Publications

High turnover rates for hydrogen sulfide allow for rapid regulation of its tissue concentrations.

Vitvitsky Victor V Kabil Omer O Banerjee Ruma R

Antioxidants & redox signaling 20120308 1

<h4>Aims</h4>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 br ...[more]

PMID: 22229551

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Project description:Hydrogen sulfide (H2S) dilates isolated arteries, and knockout of the H2S-synthesizing enzyme cystathionine γ-lyase (CSE) increases blood pressure. However, the contributions of endogenously produced H2S to blood flow regulation in specific vascular beds are unknown. Published studies in isolated arteries show that CSE production of H2S influences vascular tone more in small mesenteric arteries than in renal arteries or the aorta. Therefore, the goal of this study was to evaluate H2S regulation of blood pressure, vascular resistance, and regional blood flows using chronically instrumented rats. We hypothesized that during whole animal CSE inhibition, vascular resistance would increase more in the mesenteric than the renal circulation. Under anesthesia, CSE inhibition [β-cyanoalanine (BCA), 30 mg/kg bolus + 5 mg·kg-1·min-1 for 20 min iv) rapidly increased mean arterial pressure (MAP) more than saline administration (%Δ: saline -1.4 ± 0.75 vs. BCA 7.1 ± 1.69, P < 0.05) but did not change resistance (MAP/flow) in either the mesenteric or renal circulation. In conscious rats, BCA infusion similarly increased MAP (%Δ: saline -0.8 ± 1.18 vs. BCA 8.2 ± 2.6, P < 0.05, n = 7) and significantly increased mesenteric resistance (saline 0.9 ± 3.1 vs. BCA 15.6 ± 6.5, P < 0.05, n = 12). The H2S donor Na2S (50 mg/kg) decreased blood pressure and mesenteric resistance ,but the fall in resistance was not significant. Inhibiting CSE for multiple days with dl-proparglycine (PAG, 50 mg·kg-1·min-1 iv bolus for 5 days) significantly increased vascular resistance in both mesenteric (ratio of day 1: saline 0.86 ± 0.033 vs. PAG 1.79 ± 0.38) and renal circulations (ratio of day 1: saline 1.26 ± 0.22 vs. 1.98 ± 0.14 PAG). These results support our hypothesis that CSE-derived H2S is an important regulator of blood pressure and vascular resistance in both mesenteric and renal circulations. Furthermore, inhalation anesthesia diminishes the effect of CSE inhibition on vascular tone.NEW & NOTEWORTHY These results suggest that CSE-derived H2S has a prominent role in regulating blood pressure and blood flow under physiological conditions, which may have been underestimated in prior studies in anesthetized subjects. Therefore, enhancing substrate availability or enzyme activity or dosing with H2S donors could be a novel therapeutic approach to treat cardiovascular diseases.

Project description:By electrospinning of polycaprolactone (PCL) solutions containing N-(benzoylthio)benzamide (NSHD1), a H2S donor, fibrous scaffolds with hydrogen sulfide (H2S) releasing capability (H2S-fibers) are fabricated. The resultant microfibers are capable of releasing H2S upon immersion in aqueous solution containing biological thiols under physiological conditions. The H2S release peaks of H2S-fibers appeared at 2-4h, while the peak of donor alone showed at 45 min. H2S release half-lives of H2S-fibers were 10-20 times longer than that of donor alone. Furthermore, H2S-fibers can protect cells from H2O2 induced oxidative damage by significantly decreasing the production of intracellular reactive oxygen species (ROS). Finally, we investigated the H2S-fibers application as a wound dressing in vitro. Given that H2S has a broad range of physiological functions, H2S-fibers hold great potential for various biomedical applications.Statement of significanceHydrogen sulfide, as a gaseous messenger, plays a crucial role in many physiological and pathological conditions. Recent studies about functions of H2S suggests H2S-based therapy could be promising therapeutic strategy for many diseases, such as cardiovascular disease, arthritis, and inflammatory bowel disease. Although many H2S donors have been developed and applied for biomedical studies, most of H2S donors have the shortage that the H2S release is either too fast or uncontrollable, which poorly mimic the biological generation of H2S. By simply combining electrospinning technique with our designed biological thiols activated H2S donor, NSHD1, we fabricated H2S releasing microfibers (H2S-fibers). This H2S-fibers significantly prolonged the releasing time compared to H2S donor alone. By adjusting the electrospinning parameters, tunable releasing profiles can be achieved. Moreover, the H2S fibers can protect cardiac myoblasts H9c2 and fibroblast NIH 3T3 from oxidative damage and support their proliferation as cellular scaffolds. To our knowledge, this is the first report of electrospun fibers with H2S releasing capacity. We anticipate this H2S-releasing scaffold will have great potential for biomedical applications.

Dataset Information

High turnover rates for hydrogen sulfide allow for rapid regulation of its tissue concentrations.

Aims

Results

Innovation

Conclusion

Publications

High turnover rates for hydrogen sulfide allow for rapid regulation of its tissue concentrations.

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