Epithelial Electrolyte Transport Physiology and the Gasotransmitter Hydrogen Sulfide

Pouokam, Ervice; Althaus, Mike

doi:10.1155/2016/4723416

Cited by 26 publications

(24 citation statements)

References 106 publications

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“…The basolaterally localized Na ϩ /K ϩ -ATPase generates the electrochemical driving force for apical sodium entry via ENaC and, hence, vectorial, transepithelial sodium absorption. The precise mechanism of how H 2 S decreases Na ϩ /K ϩ -ATPase activity remains unknown (46). Studies using primary cultured alveolar epithelial and A549 cells demonstrated that hypoxia also impairs transepithelial sodium absorption due to inhibition of the Na ϩ /K ϩ -ATPase (13,34).…”

Section: Discussionmentioning

confidence: 99%

“…Exogenous H 2 S exerts prosecretory and antiabsorptive actions in epithelia, leading to net transepithelial liquid secretion (46). On the basis of the general toxicity of excess H 2 S (48) Fig.…”

Section: Perspectives and Significancementioning

confidence: 99%

“…*P Յ 0.05; Student's unpaired t-test (two-tailed). and the predominant exposure of epithelia to various exogenous H 2 S sources (e.g., microbiota), we recently suggested a concept (46) by which epithelia use their electrolyte and eventually liquid transport machinery as a defense mechanism to eliminate potentially harmful H 2 S concentrations that exceed the oxidative capacity of the epithelial cells (7,8,46). In the airways, the surface epithelium absorbs liquid that is either secreted by submucosal glands or accumulates in the upper airways due to the mucociliary elevator (55).…”

Section: Perspectives and Significancementioning

confidence: 99%

“…H 2 S is enzymatically generated in human and animal cells within amino acid (L-cysteine) metabolism by cystathionine-␥-lyase (CSE), cystathionine-␤synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3MST) (53). In the presence of oxygen, mitochondria readily metabolize the enzymatically generated H 2 S to sulfate (46); hence, biologically relevant amounts of H 2 S only appear under hypoxia. Amperometric measurements of H 2 S production in various cell homogenates (18,37,42), including H441 airway epithelial cells (1), confirmed an inverse correlation between H 2 S production and O 2 concentrations and support the hypothesis that H 2 S might be a cellular O 2 sensor (37).…”

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confidence: 99%

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Hydrogen sulfide contributes to hypoxic inhibition of airway transepithelial sodium absorption

Krause

Kutsche

Santangelo

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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In lung epithelial cells, hypoxia decreases the expression and activity of sodium-transporting molecules, thereby reducing the rate of transepithelial sodium absorption. The mechanisms underlying the sensing of hypoxia and subsequent coupling to sodium-transporting molecules remain unclear. Hydrogen sulfide (H2S) has recently been recognized as a cellular signaling molecule whose intracellular concentrations critically depend on oxygen levels. Therefore, it was questioned whether endogenously produced H2S contributes to hypoxic inhibition of sodium transport. In electrophysiological Ussing chamber experiments, hypoxia was established by decreasing oxygen concentrations in the chambers. Hypoxia concentration dependently and reversibly decreased amiloride-sensitive sodium absorption by cultured H441 monolayers and freshly dissected porcine tracheal epithelia due to inhibition of basolateral Na(+)/K(+)-ATPase. Exogenous application of H2S by the sulfur salt Na2S mimicked the effect of hypoxia and inhibited amiloride-sensitive sodium absorption by both tissues in an oxygen-dependent manner. Hypoxia increased intracellular concentrations of H2S and decreased the concentration of polysulfides. Pretreatment with the cystathionine-γ-lyase inhibitor d/l-propargylglycine (PAG) decreased hypoxic inhibition of sodium transport by H441 monolayers, whereas inhibition of cystathionine-β-synthase (with aminooxy-acetic acid; AOAA) or 3-mercaptopyruvate sulfurtransferase (with aspartate) had no effect. Inhibition of all of these H2S-generating enzymes with a combination of AOAA, PAG, and aspartate decreased the hypoxic inhibition of sodium transport by H441 cells and pig tracheae and decreased H2S production by tracheae. These data suggest that airway epithelial cells endogenously produce H2S during hypoxia, and this contributes to hypoxic inhibition of transepithelial sodium absorption.

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Section: Discussionmentioning

confidence: 99%

Section: Perspectives and Significancementioning

confidence: 99%

Section: Perspectives and Significancementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Hydrogen sulfide contributes to hypoxic inhibition of airway transepithelial sodium absorption

Krause

Kutsche

Santangelo

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In rat, guinea pig and human colon preparations, H 2 S stimulates the secretion of chloride 15 . This is either due to direct actions on ion channels and transporters within the epithelial cells 18,19 , or indirectly by stimulating enteric secretomotor neurons 20 .…”

Section: Introductionmentioning

confidence: 99%

Hydrogen sulfide stimulates CFTR in Xenopus oocytes by activation of the cAMP/PKA signalling axis

Perniss

Preiss

Nier

et al. 2017

Sci Rep

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Hydrogen sulfide (H2S) has been recognized as a signalling molecule which affects the activity of ion channels and transporters in epithelial cells. The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial anion channel and a key regulator of electrolyte and fluid homeostasis. In this study, we investigated the regulation of CFTR by H2S. Human CFTR was heterologously expressed in Xenopus oocytes and its activity was electrophysiologically measured by microelectrode recordings. The H2S-forming sulphur salt Na2S as well as the slow-releasing H2S-liberating compound GYY4137 increased transmembrane currents of CFTR-expressing oocytes. Na2S had no effect on native, non-injected oocytes. The effect of Na2S was blocked by the CFTR inhibitor CFTR_inh172, the adenylyl cyclase inhibitor MDL 12330A, and the protein kinase A antagonist cAMPS-Rp. Na2S potentiated CFTR stimulation by forskolin, but not that by IBMX. Na2S enhanced CFTR stimulation by membrane-permeable 8Br-cAMP under inhibition of adenylyl cyclase-mediated cAMP production by MDL 12330A. These data indicate that H2S activates CFTR in Xenopus oocytes by inhibiting phosphodiesterase activity and subsequent stimulation of CFTR by cAMP-dependent protein kinase A. In epithelia, an increased CFTR activity may correspond to a pro-secretory response to H2S which may be endogenously produced by the epithelium or H2S-generating microflora.

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Efficacy of Covexir® (Ferula foetida oleo‐gum) treatment in symptomatic improvement of patients with mild to moderate COVID‐19: A randomized, double‐blind, placebo‐controlled trial

Hasanpour

Safari

Mohammadpour

et al. 2022

Phytotherapy Research

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The SARS-CoV-2 COVID-19 pandemic has emerged as an unprecedented emergency state in healthcare system and global challenge. In recent decade, the function of exogenous H 2 S in the treatment of respiratory diseases has been investigated using H 2 S-donor agents. Ferula foetida is a medicinal plant that is traditionally used in respiratory diseases including asthma and viral respiratory diseases. The oleo-gum of this plant is a rich source of several organic sulfides including thiophenes, disulfides and polysulfide derivatives, which can act as H 2 S-donor agents. The purpose of this study was to investigate the efficacy of Covexir ® (F. foetida oleo-gum) treatment as a rich source of H 2 S-donor compounds in clinical presentations of patients with COVID-19.The efficacy of Covexir ® was evaluated in a randomized, double-blind, placebocontrolled trial in outpatients with COVID-19. Covexir ® could significantly inhibit cough when compared to the placebo group (p < .01 and p < 001, respectively).Moreover, there was a significant difference (p < 001) between the two groups in dyspnea symptom at follow-up interval of 7 day after receiving Covexir ® . Furthermore, on days 3 and 7, statistically significant differences were observed in myalgia, anorexia, anosmia, and sense of taste severity between two groups. Our findings revealed that Covexir ® was very safe in the treatment of COVID-19 patients with mild to moderate symptoms and it can be recommended to improve clinical presentations of patients with COVID-19 such as cough, shortness of breath, myalgia, anorexia, anosmia, and sense of taste.

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Epithelial Electrolyte Transport Physiology and the Gasotransmitter Hydrogen Sulfide

Cited by 26 publications

References 106 publications

Hydrogen sulfide contributes to hypoxic inhibition of airway transepithelial sodium absorption

Hydrogen sulfide contributes to hypoxic inhibition of airway transepithelial sodium absorption

Hydrogen sulfide stimulates CFTR in Xenopus oocytes by activation of the cAMP/PKA signalling axis

Efficacy of Covexir® (Ferula foetida oleo‐gum) treatment in symptomatic improvement of patients with mild to moderate COVID‐19: A randomized, double‐blind, placebo‐controlled trial

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