scholarly journals Hydrogen Sulfide Is a Regulator of Hemoglobin Oxygen-Carrying Capacity via Controlling 2,3-BPG Production in Erythrocytes

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Gang Wang ◽  
Yan Huang ◽  
Ningning Zhang ◽  
Wenhu Liu ◽  
Changnan Wang ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Binding Affinity ◽  
Carrying Capacity ◽  
Inhibitory Effect ◽  
Peripheral Tissues ◽  
Metabolomic Profiling ◽  
Wide Range ◽  
Mammalian Tissues ◽  
Oxygen Carrying Capacity ◽  
O2 Binding

Hydrogen sulfide (H2S) is naturally synthesized in a wide range of mammalian tissues. Whether H2S is involved in the regulation of erythrocyte functions remains unknown. Using mice with a genetic deficiency in a H2S natural synthesis enzyme cystathionine-γ-lyase (CSE) and high-throughput metabolomic profiling, we found that levels of erythrocyte 2,3-bisphosphoglycerate (2,3-BPG), an erythroid-specific metabolite negatively regulating hemoglobin- (Hb-) oxygen (O2) binding affinity, were increased in CSE knockout (Cse-/-) mice under normoxia. Consistently, the 50% oxygen saturation (P50) value was increased in erythrocytes of Cse-/- mice. These effects were reversed by treatment with H2S donor GYY4137. In the models of cultured mouse and human erythrocytes, we found that H2S directly acts on erythrocytes to decrease 2,3-BPG production, thereby enhancing Hb-O2 binding affinity. Mouse genetic studies showed that H2S produced by peripheral tissues has a tonic inhibitory effect on 2,3-BPG production and consequently maintains Hb-O2 binding affinity in erythrocytes. We further revealed that H2S promotes Hb release from the membrane to the cytosol and consequently enhances bisphosphoglycerate mutase (BPGM) anchoring to the membrane. These processes might be associated with S-sulfhydration of Hb. Moreover, hypoxia decreased the circulatory H2S level and increased the erythrocyte 2,3-BPG content in mice, which could be reversed by GYY4137 treatment. Altogether, our study revealed a novel signaling pathway that regulates oxygen-carrying capacity in erythrocytes and highlights a previously unrecognized role of H2S in erythrocyte 2,3-BPG production.

Consultation with the Specialist

1992 ◽  
Vol 13 (10) ◽  
pp. 379-380
Author(s):  
William B. Strong
Keyword(s):  
Cardiac Output ◽  
Oxygen Saturation ◽  
Carrying Capacity ◽  
Hemoglobin Concentration ◽  
Cyanotic Congenital Heart Disease ◽  
Compensatory Mechanism ◽  
Peripheral Tissues ◽  
Arterial Blood ◽  
Infant And Young Child ◽  
Oxygen Carrying Capacity

What is the likely pathophysiology of this event? What are the more common complications of hypoxemia in the older infant and young child? This clinical scenario is uncommon, but it represents one of the two feared central nervous system complications of cyanotic congenital heart disease, (ie, cerebrovascular accident and brain abscess). A uniform response to hypoxemia of cardiac etiology is the production of erythropoietin to produce more red blood cells. This is a compensatory mechanism to maintain oxygen delivery to the peripheral tissues. Normally, hemoglobin is about 96% saturated with oxygen. Therefore, the oxygen-carrying capacity of blood with a normal hemoglobin concentration of 15 g/dL is approximately 20.3 mL of oxygen per 100 mL of blood (ie, 15 g of hemoglobin x 1.35 mL of O2 per g of hemoglobin = 20.3). The oxygen content of blood equals the oxygen-carrying capacity multiplied by the oxygen saturation. At a normal oxygen saturation of 96%, the O2 content of arterial blood (Hgb 15 g/dL) equals 19.5 mL/dL (96% x 20.3 mm3/dL) or 195 mL per liter of cardiac output. The arterial O2 content of this child, assuming an average arterial saturation of 85%, will be 11.1 mL/dL. Therefore, every liter (10 dL) of cardiac output will carry 111 mL of O2 or 84 mL of O2 less than the child with a 15 g/dL hemoglobin level.

scholarly journals S-3-Carboxypropyl-l-cysteine specifically inhibits cystathionine γ-lyase–dependent hydrogen sulfide synthesis

2019 ◽  
Vol 294 (28) ◽  
pp. 11011-11022 ◽  
Author(s):  
Pramod K. Yadav ◽  
Victor Vitvitsky ◽  
Hanseong Kim ◽  
Andrew White ◽  
Uhn-Soo Cho ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Cultured Cells ◽  
Inhibitory Effect ◽  
Cleavage Reaction ◽  
Physiological Processes ◽  
Structural Framework ◽  
Wide Range ◽  
Mercaptopyruvate Sulfurtransferase ◽  
Substrate Inhibitor

Hydrogen sulfide (H2S) is a gaseous signaling molecule, which modulates a wide range of mammalian physiological processes. Cystathionine γ-lyase (CSE) catalyzes H2S synthesis and is a potential target for modulating H2S levels under pathophysiological conditions. CSE is inhibited by propargylglycine (PPG), a widely used mechanism-based inhibitor. In this study, we report that inhibition of H2S synthesis from cysteine, but not the canonical cystathionine cleavage reaction catalyzed by CSE in vitro, is sensitive to preincubation of the enzyme with PPG. In contrast, the efficacy of S-3-carboxpropyl-l-cysteine (CPC) a new inhibitor described herein, was not dependent on the order of substrate/inhibitor addition. We observed that CPC inhibited the γ-elimination reaction of cystathionine and H2S synthesis from cysteine by human CSE with Ki values of 50 ± 3 and 180 ± 15 μm, respectively. We noted that CPC spared the other enzymes involved either directly (cystathionine β-synthase and mercaptopyruvate sulfurtransferase) or indirectly (cysteine aminotransferase) in H2S biogenesis. CPC also targeted CSE in cultured cells, inhibiting transsulfuration flux by 80–90%, as monitored by the transfer of radiolabel from [35S]methionine to GSH. The 2.5 Å resolution crystal structure of human CSE in complex with the CPC-derived aminoacrylate intermediate provided a structural framework for the molecular basis of its inhibitory effect. In summary, our study reveals a previously unknown confounding effect of PPG, widely used to inhibit CSE-dependent H2S synthesis, and reports on an alternative inhibitor, CPC, which could be used as a scaffold to develop more potent H2S biogenesis inhibitors.

scholarly journals Adrenalin-Induced Na+/H+ Exchange in' Trout Erythrocytes and its Effects Upon Oxygen-Carrying Capacity

1985 ◽  
Vol 118 (1) ◽  
pp. 229-246 ◽  
Author(s):  
A. R. COSSINS ◽  
P. A. RICHARDSON
Keyword(s):  
Steady State ◽  
Intracellular Ph ◽  
Carrying Capacity ◽  
Extracellular Ph ◽  
Extracellular Medium ◽  
Root Effect ◽  
Fish Blood ◽  
Wide Range ◽  
Oxygen Carrying Capacity ◽  
Normal Relationship

Addition of adrenalin (10−4moll−1) to trout erythrocytes in an unbuffered saline resulted in a rapid acidification of the extracellular medium. This process was inhibited by amiloride (K½10−4moll−1) and by the removal of extracellular Na+. The rate of acidification was a saturable function of extracellular Na+ concentration. When extracellular pH was maintained constant by continual titration with KOH, adrenalin induced a transient burst of H+ efflux. During this period the loss of cellular H+ equivalents was approximately equal to the net gain of Na+, providing evidence for a Na+/H+ exchange with a stoichiometry of 1. The steady state following stimulation with adrenalin could be disturbed by changes in extracellular pH. After the addition of adrenalin, intracellular pH (pHi) was increased by 0.2-0.3 units but did not exceed extracellular pH, as required if the Na+ and H+ concentration ratios came into equilibrium. The increase in pHi in stimulated compared with control cells was maintained approximately constant over a wide range of pHo, suggesting that pH equilibration by the Jacob-Stewart cycle was operating normally and that the activation of Na+/H+ exchange provides an offset to the normal relationship between pHi and pHo. The steady state results from a balance of an increase Na+/H+ and CI−/HCO3− exchange with an increased rate of Na+ pumping and next KCl efflux. In a buffered saline, adrenalin caused a 22–46% increase in the oxygen-carrying capacity of trout erythrocytes. It is suggested that this was due to a Root effect of trout haemoglobin caused by cellular alkalinization when the Na+/H+ exchange mechanism was activiated. This observation suggests that many published values for oxygencarrying capacity of fish blood require re-evaluation.

scholarly journals Albizia chinensis bark extract ameliorates the genotoxic effect of cyclophosphamide

2020 ◽  
Vol 44 (1) ◽  
Author(s):  
Marian Nabil ◽  
Entesar E. Hassan ◽  
Neven S. Ghaly ◽  
Fawzia A. Aly ◽  
Farouk R. Melek ◽  
...  
Keyword(s):  
Folk Medicine ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Bark Extract ◽  
Repeated Treatment ◽  
Mouse Bone Marrow ◽  
Sperm Abnormalities ◽  
Wide Range ◽  
Different Doses

Abstract Background The genus Albizia (Leguminoseae) is used in folk medicine for the treatment of a wide range of ailments. Recently, saponins from plant origin have attracted much attention. Saponins are recorded to have a broad range of biological and pharmacological activities. This study was performed to evaluate the protective role of Albizia chinensis bark methanolic extract (MEAC) against the genotoxicity induced by cyclophosphamide (CP) using different mutagenic parameters. Results The results showed that MEAC induced an inhibitory effect against chromosomal aberrations of CP in mouse bone marrow and spermatocytes. Such effect was found to be significant (p < 0.01) with a dose of 100 mg/kg treated once for 24 h and also after repeated treatment at a dose of 25 mg/kg for 7 days. In sperm abnormalities, the protective effect of Albizia extract showed a dose-related relationship. Different doses of MEAC (25, 50, and 100 mg/kg) significantly (p < 0.01) ameliorated sperm abnormalities induced by CP dose-dependently. The percentage of sperm abnormalities was decreased to 5.14 ± 0.72 in the group of animals treated with CP plus MEAC (100 mg/kg) indicating an inhibitory effect of about 50%. Conclusion MEAC at the doses examined was non-genotoxic compared to control (negative) and exhibited a protective role against CP genotoxicity.

Layer-by-layer assembly of hemoglobin-coated microspheres for enhancing the oxygen carrying capacity

RSC Advances ◽  
2016 ◽  
Vol 6 (65) ◽  
pp. 59984-59987 ◽  
Author(s):  
Lijun Sun ◽  
Yannan Lu ◽  
Zhongqin Pan ◽  
Tingting Wu ◽  
Xiaojun Liu ◽  
...  
Keyword(s):  
Carrying Capacity ◽  
Layer By Layer ◽  
Layer By Layer Assembly ◽  
Oxygen Carrying Capacity ◽  
Layer Assembly

Hemoglobin-coated microspheres with one layer and five layers were fabricated by layer-by-layer assembly.

scholarly journals Desethylamiodarone antagonizes the effect of thyroid hormone at the molecular level

2001 ◽  
pp. 59-64 ◽  
Author(s):  
F Bogazzi ◽  
L Bartalena ◽  
S Brogioni ◽  
A Burelli ◽  
F Raggi ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Molecular Mechanisms ◽  
Thyroid Hormone Receptor ◽  
Molecular Level ◽  
Inhibitory Effect ◽  
Mobility Shift ◽  
Down Regulation ◽  
Nih3t3 Cells ◽  
Peripheral Tissues

OBJECTIVE: To evaluate the molecular mechanisms of the inhibitory effects of amiodarone and its active metabolite, desethylamiodarone (DEA) on thyroid hormone action. MATERIALS AND METHODS: The reporter construct ME-TRE-TK-CAT or TSHbeta-TRE-TK-CAT, containing the nucleotide sequence of the thyroid hormone response element (TRE) of either malic enzyme (ME) or TSHbeta genes, thymidine kinase (TK) and chloramphenicol acetyltransferase (CAT) was transiently transfected with RSV-TRbeta into NIH3T3 cells. Gel mobility shift assay (EMSA) was performed using labelled synthetic oligonucleotides containing the ME-TRE and in vitro translated thyroid hormone receptor (TR)beta. RESULTS: Addition of 1 micromol/l T4 or T3 to the culture medium increased the basal level of ME-TRE-TK-CAT by 4.5- and 12.5-fold respectively. Amiodarone or DEA (1 micromol/l) increased CAT activity by 1.4- and 3.4-fold respectively. Combination of DEA with T4 or T3 increased CAT activity by 9.4- and 18.9-fold respectively. These data suggested that DEA, but not amiodarone, had a synergistic effect with thyroid hormone on ME-TRE, rather than the postulated inhibitory action; we supposed that this was due to overexpression of the transfected TR into the cells. When the amount of RSV-TRbeta was reduced until it was present in a limited amount, allowing competition between thyroid hormone and the drug, addition of 1 micromol/l DEA decreased the T3-dependent expression of the reporter gene by 50%. The inhibitory effect of DEA was partially due to a reduced binding of TR to ME-TRE, as assessed by EMSA. DEA activated the TR-dependent down-regulation by the negative TSH-TRE, although at low level (35% of the down-regulation produced by T3), whereas amiodarone was ineffective. Addition of 1 micromol/l DEA to T3-containing medium reduced the T3-TR-mediated down-regulation of TSH-TRE to 55%. CONCLUSIONS: Our results demonstrate that DEA, but not amiodarone, exerts a direct, although weak, effect on genes that are regulated by thyroid hormone. High concentrations of DEA antagonize the action of T3 at the molecular level, interacting with TR and reducing its binding to TREs. This effect may contribute to the hypothyroid-like effect observed in peripheral tissues of patients receiving amiodarone treatment.

scholarly journals EVALUATION OF A STROMA-FREE HEMOGLOBIN SOLUTION FOR USE AS A PLASMA EXPANDER

1967 ◽  
Vol 126 (6) ◽  
pp. 1127-1142 ◽  
Author(s):  
S. Frederick Rabiner ◽  
J. Raymond Helbert ◽  
Harry Lopas ◽  
Lila H. Friedman
Keyword(s):  
Carrying Capacity ◽  
Vital Signs ◽  
Free Hemoglobin ◽  
Hemoglobin Solution ◽  
Plasma Expander ◽  
Chronic Effects ◽  
Coagulant Activity ◽  
Methemoglobin Formation ◽  
Oxygen Carrying Capacity ◽  
Acute And Chronic Effects

The preparation of large quantities of a stable, stroma-free hemoglobin solution without coagulant activity is described. Following infusion of this solution into phlebotomized dogs, there is no methemoglobin formation, no adverse effects on vital signs, and no demonstrable activation of blood coagulation. The hemoglobin maintains its oxygen-carrying capacity and liberates oxygen into tissues. Acute and chronic effects on renal function following infusion of this preparation were also studied and no effect on clearance of urea, creatinine, or P.A.H. could be demonstrated. There was no change in urinary output and histological sections revealed no lesions attributable to hemoglobin toxicity. It is concluded that a stroma-free hemoglobin solution may have use as a plasma expander.

scholarly journals Oxygen carrying capacity of completely artificial red blood cell substitute : Liposome-embedded-heme

1990 ◽  
Vol 4 (6) ◽  
pp. 676-680
Author(s):  
Koichi Kobayashi ◽  
Masazumi Watanabe ◽  
Toshinori Hashizume ◽  
Masabumi Kawamura ◽  
Ryoichi Kato ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Carrying Capacity ◽  
Oxygen Carrying Capacity

Cholecystokinin octapeptide analogues suppress food intake via central CCK-A receptors in mice

1993 ◽  
Vol 265 (3) ◽  
pp. R481-R486 ◽  
Author(s):  
Y. Hirosue ◽  
A. Inui ◽  
A. Teranishi ◽  
M. Miura ◽  
M. Nakajima ◽  
...  
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Rank Order ◽  
Peripheral Circulation ◽  
Inhibitory Effect ◽  
Peripheral Tissues ◽  
Cholecystokinin Octapeptide ◽  
The Central Nervous System ◽  
The Difference ◽  
The Brain

To examine the mechanism of the satiety-producing effect of cholecystokinin (CCK) in the central nervous system, we compared the potency of intraperitoneally (ip) or intracerebroventricularly (icv) administered CCK-8 and its analogues on food intake in fasted mice. The icv administration of a small dose of CCK-8 (0.03 nmol/brain) or of Suc-(Thr28, Leu29, MePhe33)-CCK-7 (0.001 nmol/brain) suppressed food intake for 20 min, whereas CCK-8 (1 nmol/kg, which is equivalent to 0.03 nmol/brain) or Suc-(Thr28, Leu29, MePhe33)-CCK-7 (1 nmol/kg) had satiety effect after ip administration. Dose-response studies indicated the following rank order of potency: Suc-CCK-7 > or = Suc-(Thr28, Leu29, MePhe33)-CCK-7 > or = CCK-8 > or = (Nle28,31)-CCK-8 >> desulfated CCK-8 = CCK-4 = 0 in the case of ip administration and Suc-(Thr28, Leu29, MePhe33)-CCK-7 >> Suc-CCK-7 > or = CCK-8 > or = (Nle28,31)-CCK-8 >> desulfated CCK-8 = CCK-4 = 0 in the case of icv administration. The selective CCK-A receptor antagonist MK-329 reversed the inhibitory effect of the centrally as well as peripherally administered CCK-8, or of Suc-(Thr28, Leu29, MePhe33)-CCK-7, whereas the selective CCK-B receptor antagonist L-365260 did not. The icv administered CCK-8 did not appear in the peripheral circulation. These findings suggest the participation of CCK-A receptors in the brain in mediating the satiety effect of CCK and the difference in CCK-A receptors in the brain and peripheral tissues.

scholarly journals The Role of Host-Generated H2S in Microbial Pathogenesis: New Perspectives on Tuberculosis

2020 ◽  
Vol 10 ◽  
Author(s):  
Md. Aejazur Rahman ◽  
Joel N. Glasgow ◽  
Sajid Nadeem ◽  
Vineel P. Reddy ◽  
Ritesh R. Sevalkar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Host Immunity ◽  
Microbial Pathogens ◽  
Microbial Pathogenesis ◽  
Enzymatic Production ◽  
Growth And Survival ◽  
Wide Range

For centuries, hydrogen sulfide (H2S) was considered primarily as a poisonous gas and environmental hazard. However, with the discovery of prokaryotic and eukaryotic enzymes for H2S production, breakdown, and utilization, H2S has emerged as an important signaling molecule in a wide range of physiological and pathological processes. Hence, H2S is considered a gasotransmitter along with nitric oxide (•NO) and carbon monoxide (CO). Surprisingly, despite having overlapping functions with •NO and CO, the role of host H2S in microbial pathogenesis is understudied and represents a gap in our knowledge. Given the numerous reports that followed the discovery of •NO and CO and their respective roles in microbial pathogenesis, we anticipate a rapid increase in studies that further define the importance of H2S in microbial pathogenesis, which may lead to new virulence paradigms. Therefore, this review provides an overview of sulfide chemistry, enzymatic production of H2S, and the importance of H2S in metabolism and immunity in response to microbial pathogens. We then describe our current understanding of the role of host-derived H2S in tuberculosis (TB) disease, including its influences on host immunity and bioenergetics, and on Mycobacterium tuberculosis (Mtb) growth and survival. Finally, this review discusses the utility of H2S-donor compounds, inhibitors of H2S-producing enzymes, and their potential clinical significance.

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