title: Divergent behavior of hydrogen sulfide pools and of the sulfur metabolite lanthionine, a novel uremic toxin, in dialysis patients.
abstract: Dialysis patients display a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity. Among uremic toxins, homocysteine and cysteine are both substrates of cystathionine β-synthase and cystathionine γ-lyase in hydrogen sulfide biosynthesis, leading to the formation of two sulfur metabolites, lanthionine and homolanthionine, considered stable indirect biomarkers of its production. Hydrogen sulfide is involved in the modulation of multiple pathophysiological responses. In uremia, we have demonstrated low plasma total hydrogen sulfide levels, due to reduced cystathionine γ-lyase expression. Plasma hydrogen sulfide levels were measured in hemodialysis patients and healthy controls with three different techniques in comparison, allowing to discern the different pools of this gas. The protein-bound (the one thought to be the most active) and acid-labile forms are significantly decreased, while homolanthionine, but especially lanthionine, accumulate in the blood of uremic patients. The hemodialysis regimen plays a role in determining sulfur compounds levels, and lanthionine is partially removed by a single dialysis session. Lanthionine inhibits hydrogen sulfide production in cell cultures under conditions comparable to in vivo ones. We therefore propose that lanthionine is a novel uremic toxin. The possible role of high lanthionine as a contributor to the genesis of hyperhomocysteinemia in uremia is discussed.
authors.affiliation: First Division of Nephrology, Department of Cardio-thoracic and Respiratory Sciences, Second University of Naples, School of Medicine, Via Pansini 5, Ed. 17, Naples 80131, Italy. Electronic address: alessandra.perna@unina2.it.
authors.forename: Alessandra F
authors.initials: AF
authors.lastname: Perna
authors.affiliation: First Division of Nephrology, Department of Cardio-thoracic and Respiratory Sciences, Second University of Naples, School of Medicine, Via Pansini 5, Ed. 17, Naples 80131, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Di Nunzio
authors.affiliation: Ceinge, Advanced Biotechnologies and Department of Chemical Sciences, "Federico II" University, Naples 80100, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Amoresano
authors.affiliation: Ceinge, Advanced Biotechnologies and Department of Chemical Sciences, "Federico II" University, Naples 80100, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pane
authors.affiliation: Ceinge, Advanced Biotechnologies and Department of Chemical Sciences, "Federico II" University, Naples 80100, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Fontanarosa
authors.affiliation: Ceinge, Advanced Biotechnologies and Department of Chemical Sciences, "Federico II" University, Naples 80100, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Pucci
authors.affiliation: Department of Biochemistry and Biophysics and General Pathology, Second University of Naples, School of Medicine, Via De Crecchio 7, Naples 80138, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Vigorito
authors.affiliation: First Division of Nephrology, Department of Cardio-thoracic and Respiratory Sciences, Second University of Naples, School of Medicine, Via Pansini 5, Ed. 17, Naples 80131, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cirillo
authors.affiliation: First Division of Nephrology, Department of Cardio-thoracic and Respiratory Sciences, Second University of Naples, School of Medicine, Via Pansini 5, Ed. 17, Naples 80131, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Zacchia
authors.affiliation: First Division of Nephrology, Department of Cardio-thoracic and Respiratory Sciences, Second University of Naples, School of Medicine, Via Pansini 5, Ed. 17, Naples 80131, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Trepiccione
authors.affiliation: Department of Biochemistry and Biophysics and General Pathology, Second University of Naples, School of Medicine, Via De Crecchio 7, Naples 80138, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Ingrosso
mesh_terms: D000328:Adult; D000368:Aged; D000409:Alanine / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000097:blood*; D020138:Hyperhomocysteinemia / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D013440:Sulfides / Q000097:blood*; D014511:Uremia / Q000097:blood* / Q000628:therapy*
chemical_list: D013440:Sulfides; C001520:lanthionine; D000409:Alanine; D006862:Hydrogen Sulfide
keywords: Hemodialysis; Homocysteine; Homolanthionine; Hydrogen sulfide; Lanthionine; Uremic toxins