Chondroitin

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

Pecora F, Gualeni B, Forlino A, Superti-Furga A, Tenni R, Cetta G, Rossi A.

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 diastrophic dysplasia sulfate transporter chondrodysplasias. In this study we have considered the contribution of cysteine and cysteine derivatives to in vivo macromolecular sulfation of cartilage by using the mouse model of diastrophic dysplasia we have recently generated. 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 one week of newborn mutant and wild-type mice with hypodermic N-acetylcysteine. The relative amount of sulfated disaccharides increased in mutant mice treated with N-acetylcysteine compared to the placebo group, indicating an increase of proteoglycan sulfation due to N-acetylcysteine catabolism, although pharmacokinetic studies demonstrated that the drug was rapidly removed from the blood stream. In conclusion cysteine contribution to cartilage proteoglycan sulfation in vivo is minimal in physiologic condition even if extracellular sulfate availability is low; however the contribution of thiols to sulfation becomes significant by increasing their plasma concentration.

PMID: 16719839 [PubMed - as supplied by publisher