Hydrogen sulphide-generating pathways in haemodialysis patients: a study on relevant metabolites and transcriptional regulation of genes encoding for key enzymes

Perna, Alessandra F.; Luciano, Maria Grazia; Ingrosso, Diego; Pulzella, Paola; Sepe, Immacolata; Lanza, Diana; Violetti, Eleonora; Capasso, Rosanna; Lombardi, Cinzia; Santo, Natale G. De

doi:10.1093/ndt/gfp378

Cited by 77 publications

(81 citation statements)

References 42 publications

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“…The prediction would be that hydrogen sulfide generation is reduced in the kidney in diabetes. Previous studies have shown that plasma hydrogen sulfide level is lower in human subjects with type 2 diabetes (48,49) and in end stage kidney disease patients on hemodialysis (50). Relevant to diabetic kidney disease, hydrogen sulfide levels in the kidney are reduced in a chemical model of type 1 diabetes in the rat (8).…”

Section: Discussionmentioning

confidence: 98%

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

Lee

Mariappan

Féliers

et al. 2012

Journal of Biological Chemistry

112

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Section: Discussionmentioning

confidence: 98%

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

Lee

Mariappan

Féliers

et al. 2012

Journal of Biological Chemistry

112

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“…Third, chronic administration of CSE inhibitor propargylglycine induces nephropathy. Finally, blood H 2 S and sulfhemoglobin levels, as well as CSE expression in blood mononuclear cells, are reduced in end-stage renal disease patients compared with healthy controls, indicating that chronic renal failure is a state of H 2 S deficiency (Perna et al, 2009). …”

Section: H 2 S Hypoxia and Chronic Kidney Diseasementioning

confidence: 99%

Hypoxia in the Renal Medulla: Implications for Hydrogen Sulfide Signaling

Bełtowski

2010

J Pharmacol Exp Ther

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Hydrogen sulfide (H 2 S) is enzymatically generated in mammalian tissues from either L-cysteine or L-homocysteine. H 2 S possesses multiple biological activities, including regulation of vascular tone and blood pressure. Hydrogen sulfide produced in endothelial cells, vascular smooth muscle cells, and perivascular adipose tissue dilates blood vessels by activating ATP-sensitive potassium channels. In addition, H 2 S produced locally within the kidney stimulates natriuresis and diuresis by increasing glomerular filtration and inhibiting tubular sodium reabsorption. Because H 2 S is oxidized in mitochondria in pO 2 -dependent manner and ambient pO 2 is physiologically low in the renal medulla, it is expected that the activity of H 2 S is higher in the medullary region than the cortical region. H 2 S, accumulating in increased amounts in the renal medulla under hypoxic conditions, may function as an oxygen sensor that restores O 2 balance by increasing medullary blood flow, reducing energy requirements for tubular transport, and directly inhibiting mitochondrial respiration. Hypoxia is an important pathogenic factor in many renal diseases, such as ischemia/reperfusion-or nephrotoxin-induced acute renal failure, progression of chronic nephropathies, diabetic nephropathy, and arterial hypertension. Deficiency of endogenous H 2 S may contribute to the pathogenesis of these pathologies by compromising medullary oxygenation, and administration of H 2 S donors may be of therapeutic value in these disorders.Studies performed during the last decade indicate that, apart from NO and CO, H 2 S is the third "gasotransmitter" involved in the regulation of various physiological functions, including vascular tone and blood pressure, inflammatory reaction, neurotransmission and gastrointestinal system function. H 2 S is enzymatically synthesized in three metabolic pathways (Fig. 1): 1) desulfhydration of L-cysteine or L-homocysteine by cystathionine ␥-lyase (CSE, EC 4.4.1.1), 2) desulfhydration of L-cysteine by cystathionine ␤-synthase (CBS, EC 4.2.1.22), and 3) transamination of L-cysteine by cysteine aminotransferase (identical with aspartate aminotransferase) to 3-mercaptopyruvate, followed by its desulfhydration to pyruvate by 3-mercaptopyruvate sulfurtransferase (3-MST, EC 2.8.1.2). Hydrogen sulfide activates ATP-sensitive potassium channels (K ATP ) in various cells, although many other signaling mechanisms have also been described. H 2 S is inactivated by binding to hemoglobin to form sulfhemoglobin, excretion in exhaled air, and, first and foremost, oxidation in mitochondria. Many studies addressed the role of H 2 S in the regulation of vascular tone and blood pressure. Indeed, it is suggested that H 2 S deficiency may contribute to the pathogenesis of arterial hypertension both in experimental animal models and in humans. Recently, renal synthesis and activity of H 2 S have been characterized (Xia et al., 2009). Because renal sodium handling has a prominent role in the long-term regulation of blood pressure (apart...

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“…125 Red cell sulfhemoglobin (a putative marker of chronic H 2 S exposure) levels, is low in this patient population, and is accompanied by high plasma homocysteine and cysteine levels, with a significant negative correlation between cysteine and H 2 S. Gene expression of CSE in blood mononuclear cells is significantly lower, realizing a condition in which a transcriptional down-regulation of the gene encoding for a key H 2 S-producing enzyme is present. 126 These findings are in line with what was Figure 3.…”

Section: Ckd Progression and Complicationsmentioning

confidence: 83%

Gases as Uremic Toxins: Is There Something in the Air?

Jankowski

Westhof

Vaziri

et al. 2014

Seminars in Nephrology

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Summary: The field of uremic toxicity comprises the study of a large number of different substances, classified in relation to various characteristics, for example, protein-binding, dimensions, and so forth. The endogenous compounds of a gaseous nature have received much attention lately from the scientific community because of their increasingly recognized importance in health and disease. Among these substances, some are uremic toxins per se, others are related to uremic toxins, or can become toxic under some circumstances. We divided them into two broad categories: organic and inorganic compounds. Among the organic compounds are phenols, indols, 2-methoxyresorcinol, p-hydroxy hippuric acid and phenyl acetic acid, trimethylamine, and dimethylamine; among the inorganic solutes are ammonia, nitric oxide, carbon monoxide, and hydrogen sulfide. In this article, these substances are described in relation to the elements that they affect or by which they are affected in uremia, which are the blood, breath, stools, and the gastrointestinal tract. In addition, the effect of the dialysis procedure on exhaled gases are described. Semin Nephrol 34:135-150 C 2014 Published by Elsevier Inc.

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Hydrogen sulphide-generating pathways in haemodialysis patients: a study on relevant metabolites and transcriptional regulation of genes encoding for key enzymes

Cited by 77 publications

References 42 publications

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

Hypoxia in the Renal Medulla: Implications for Hydrogen Sulfide Signaling

Gases as Uremic Toxins: Is There Something in the Air?

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