In vivo contribution of amino acid sulfur to cartilage proteoglycan sulfation.

Détails

ID Serval
serval:BIB_4301E81BE975
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
In vivo contribution of amino acid sulfur to cartilage proteoglycan sulfation.
Périodique
Biochemical Journal
Auteur(s)
Pecora F., Gualeni B., Forlino A., Superti-Furga A., Tenni R., Cetta G., Rossi A.
ISSN
1470-8728 (Electronic)
ISSN-L
0264-6021
Statut éditorial
Publié
Date de publication
2006
Volume
398
Numéro
3
Pages
509-514
Langue
anglais
Résumé
Cytoplasmic sulfate for sulfation reactions may be derived either from extracellular fluids or from catabolism of sulfur-containing amino acids and other thiols. In vitro studies have pointed out the potential relevance of sulfur-containing amino acids as sources for sulfation when extracellular sulfate concentration is low or when its transport is impaired such as in DTDST [DTD (diastrophic dysplasia) sulfate transporter] chondrodysplasias. In the present study, we have considered the contribution of cysteine and cysteine derivatives to in vivo macromolecular sulfation of cartilage by using the mouse model of DTD we have recently generated [Forlino, Piazza, Tiveron, Della Torre, Tatangelo, Bonafe, Gualeni, Romano, Pecora, Superti-Furga et al. (2005) Hum. Mol. Genet. 14, 859-871]. By intraperitoneal injection of [35S]cysteine in wild-type and mutant mice and determination of the specific activity of the chondroitin 4-sulfated disaccharide in cartilage, we demonstrated that the pathway by which sulfate is recruited from the intracellular oxidation of thiols is active in vivo. To check whether cysteine derivatives play a role, sulfation of cartilage proteoglycans was measured after treatment for 1 week of newborn mutant and wild-type mice with hypodermic NAC (N-acetyl-L-cysteine). The relative amount of sulfated disaccharides increased in mutant mice treated with NAC compared with the placebo group, indicating an increase in proteoglycan sulfation due to NAC catabolism, although pharmacokinetic studies demonstrated that the drug was rapidly removed from the bloodstream. In conclusion, cysteine contribution to cartilage proteoglycan sulfation in vivo is minimal under physiological conditions even if extracellular sulfate availability is low; however, the contribution of thiols to sulfation becomes significant by increasing their plasma concentration.
Mots-clé
Acetylcysteine, Amino Acid Substitution, Amino Acids/metabolism, Animals, Anion Transport Proteins, CHO Cells, Carrier Proteins/genetics, Carrier Proteins/metabolism, Cartilage/chemistry, Cricetinae, Gene Expression Regulation, Membrane Transport Proteins/genetics, Membrane Transport Proteins/metabolism, Mice, Mice, Transgenic, Mutation, Proteoglycans/chemistry, Proteoglycans/metabolism, Sulfates/metabolism, Sulfhydryl Compounds/metabolism, Sulfur/metabolism
Pubmed
Web of science
Création de la notice
14/03/2011 17:08
Dernière modification de la notice
03/03/2018 16:39
Données d'usage