Hydrogen sulfide causes vanilloid receptor 1‐mediated neurogenic inflammation in the airways

Trevisani, Marcello; Patacchini, Riccardo; Nicoletti, Paola; Gatti, Raffaele; Gazzieri, David; Lissi, Nicola; Zagli, Giovanni; Créminon, Christophe; Geppetti, Pierangelo; Harrison, Selena

doi:10.1038/sj.bjp.0706277

Cited by 142 publications

(120 citation statements)

References 53 publications

(76 reference statements)

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“…These differences could be due to increased small airway sensitivity to H 2 S and/or due to the closed conditions in the study by Castro-Piedras and PerezZoghbi (18), which prevented H 2 S volatilization. Conversely, much higher, H 2 S concentrations (EC 50 = 1.3 mM) produce a dose-dependent contraction in guinea pig main bronchae and distal trachea that appears to be mediated by activation of vanilloid neurons (171). We (Olson, unpublished) have also observed H 2 S relaxation of bovine bronchioles in the range reported by Kubo et al (80).…”

Section: Mechanical Effects On Airway Smooth Musclesupporting

confidence: 62%

Hydrogen sulfide as an oxygen sensor

Olson

2013

Clinical Chemistry and Laboratory Medicine

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Significance: Although oxygen (O 2 )-sensing cells and tissues have been known for decades, the identity of the O 2 -sensing mechanism has remained elusive. Evidence is accumulating that O 2 -dependent metabolism of hydrogen sulfide (H 2 S) is this enigmatic O 2 sensor. Recent Advances: The elucidation of biochemical pathways involved in H 2 S synthesis and metabolism have shown that reciprocal H 2 S/O 2 interactions have been inexorably linked throughout eukaryotic evolution; there are multiple foci by which O 2 controls H 2 S inactivation, and the effects of H 2 S on downstream signaling events are consistent with those activated by hypoxia. H 2 S-mediated O 2 sensing has been demonstrated in a variety of O 2 -sensing tissues in vertebrate cardiovascular and respiratory systems, including smooth muscle in systemic and respiratory blood vessels and airways, carotid body, adrenal medulla, and other peripheral as well as central chemoreceptors. Critical Issues: Information is now needed on the intracellular location and stoichometry of these signaling processes and how and which downstream effectors are activated by H 2 S and its metabolites. Future Directions: Development of specific inhibitors of H 2 S metabolism and effector activation as well as cellular organelle-targeted compounds that release H 2 S in a timeor environmentally controlled way will not only enhance our understanding of this signaling process but also provide direction for future therapeutic applications. Antioxid. Redox Signal. 22, 377-397.

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Section: Mechanical Effects On Airway Smooth Musclesupporting

confidence: 62%

Hydrogen sulfide as an oxygen sensor

Olson

2013

Clinical Chemistry and Laboratory Medicine

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“…In isolated murine pancreatic acinar cells, NaSH induced, but PAG inhibited, SP release and NK1R/PPT-A gene expression. Furthermore, in the isolated guinea pig airway, NaSH induced the release of SP and CGRP from sensory nerve terminals, and led to airway constriction through capsaicin and NKR1/NKR2-transient receptor potential vanilloid 1 (TRPV1)-dependent pathways [73,74]. Similarly, in isolated rat bladder [75] and rat detrusor muscle [76], NaSH induced tachykin release from caspaicin-sensitive primary afferent neurons, leading to smooth muscle contraction.…”

Section: Role For H 2 S In Neurogenic Inflammation?mentioning

confidence: 99%

Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising

Whiteman

Winyard

2011

Expert Review of Clinical Pharmacology

272

232

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“…Traditionally regarded as a toxic gas, H 2 S is the newest member of the family of biological gasotransmitters and appears to function both as a neuromodulator in the central nervous system and as a vasodilator of smooth muscle cells in the vascular system (9,10). In addition, H 2 S also plays an important role in inflammation, although the mechanism by which this occurs, is controversial (11)(12)(13)(14).…”

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confidence: 99%

Kinetic Properties of Polymorphic Variants and Pathogenic Mutants in Human Cystathionine γ-Lyase

2008

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Human cystathionine-γ-lyase (CGL) is a pyridoxal-5′-phosphate (PLP)-dependent enzyme, which functions in the transsulfuration pathway that converts homocysteine to cysteine. In addition, CGL is one of two major enzymes that can catalyze the formation of hydrogen sulfide, an important gaseous signaling molecule. Recently, several mutations in CGL have been described in patients with cystathioninuria, a rare but poorly understood genetic disease. Moreover, a common single nucleotide polymorphism in CGL, c.1364G>T that converts serine at position 403 to isoleucine, has been linked to elevated plasma homocysteine levels. In this study, we have characterized the pathogenic T67I and Q240E missense mutations and the polymorphic variants at amino acid residues 403 using kinetic and spectrophotometric methods. We report that the polymorphism does not influence the cofactor content of the enzyme or its steady-state kinetic properties. In contrast, the T67I mutant exhibits a 3.5-fold decrease in V max compared to that of wild-type CGL, while the Q240E mutant exhibits a 70-fold decrease in V max . The K M s for cystathionine for both pathogenic mutants are comparable to that of wild type CGL. The PLP content of the T67I and Q240E mutants were about 4-fold and 80-fold lower than that of wild-type enzyme, respectively. Preincubation of the T67I mutant with PLP restored activity to wild-type levels while the same treatment resulted in only partial restoration of activity of the Q240E mutant. These results reveal that both mutations weaken the affinity for PLP and suggest that cystathionuric patients with these mutations should be responsive to pyridoxine therapy.The mammalian transsulfuration pathway represents one of two major metabolic routes for the removal of homocysteine, which at elevated levels, is an independent risk factor for cardiovascular diseases and other complex disorders (1,2). Cystathionine γ-lyase (CGL 1 ), the second enzyme in the transsulfuration pathway, catalyzes the conversion of † This work was supported in part by a grant from the National Institutes of Health (HL58984 to R.B.) and by an American Heart Association Postdoctoral Fellowship to W.Z.

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Hydrogen sulfide causes vanilloid receptor 1‐mediated neurogenic inflammation in the airways

Cited by 142 publications

References 53 publications

Hydrogen sulfide as an oxygen sensor

Hydrogen sulfide as an oxygen sensor

Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising

Kinetic Properties of Polymorphic Variants and Pathogenic Mutants in Human Cystathionine γ-Lyase

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