title: Hydrogen sulphide-generating pathways in haemodialysis patients: a study on relevant metabolites and transcriptional regulation of genes encoding for key enzymes.
abstract: BACKGROUND
  Hydrogen sulphide, H(2)S, is the third endogenous gas with putative cardiovascular properties, after nitric oxide and carbon monoxide. H(2)S is a vasorelaxant, while H(2)S deficiency is implicated in the pathogenesis of hypertension and atherosclerosis. Cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (MPS) catalyze H(2)S formation, with different relative efficiencies. Chronic kidney disease (CKD) is characterized by elevation of both plasma homocysteine and cysteine, which are substrates of these enzymes, and by a high prevalence of hypertension and cardiovascular mortality, particularly in the haemodialysis stage. It is possible that the H(2)S-generating pathways are altered as well in this patient population.
  
  
  METHODS
  Plasma H(2)S levels were measured with a common spectrophotometric method. This method detects various forms of H(2)S, protein-bound and non-protein-bound. Blood sulphaemoglobin, a marker of chronic exposure to H(2)S, was also measured, as well as related sulphur amino acids, vitamins and transcriptional levels of relevant genes, in haemodialysis patients and compared to healthy controls.
  
  
  RESULTS
  Applying the above-mentioned methodology, H(2)S levels were found to be decreased in patients. Sulphaemoglobin levels were significantly lower as well. Plasma homocysteine and cysteine were significantly higher; vitamin B(6), a cofactor in H(2)S biosynthesis, was not different. H(2)S correlated negatively with cysteine levels. CSE expression was significantly downregulated in haemodialysis patients.
  
  
  CONCLUSIONS
  Transcriptional deregulation of genes encoding for H(2)S-producing enzymes is present in uraemia. Although the specificity of the method employed for H(2)S detection is low, the finding that H(2)S is decreased is complemented by the lower sulphhaemoglobin levels. Potential implications of this study relate to the pathogenesis of the uraemic syndrome manifestations, such as hypertension and atherosclerosis.
authors: First Division of Nephrology, Department of Clinical and Experimental Internal Medicine, via Pansini 5, Second University of Medicine, 80138 Naples, Italy. alessandra.perna@unina2.it
authors: Alessandra F
authors: AF
authors: Perna
authors: Maria Grazia
authors: MG
authors: Luciano
authors: Diego
authors: D
authors: Ingrosso
authors: Paola
authors: P
authors: Pulzella
authors: Immacolata
authors: I
authors: Sepe
authors: Diana
authors: D
authors: Lanza
authors: Eleonora
authors: E
authors: Violetti
authors: Rosanna
authors: R
authors: Capasso
authors: Cinzia
authors: C
authors: Lombardi
authors: Natale G
authors: NG
authors: De Santo
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000201:enzymology* / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D014158:Transcription, Genetic
chemical_list: D006862:Hydrogen Sulfide