Molybdate impairs glycosaminoglycan sulfation in rat cartilage.
The mechanism by which molybdate produces joint and bone deformities is not known. However, we recently reported that molybdate decreases the sulfation of acetaminophen in rat liver. Therefore, the purpose of the present study was to determine the effect of molybdate on the sulfation of glycosaminoglycans (GAGS) and whether manganese-induced joint and bone deformities might be due to this mechanism. Molybdate (15 mmol/kg, po) did not alter total GAG content in patella and articular cartilage of rats assayed 24 hr after administration. Nevertheless, [35S]sulfate uptake into both patella and articular cartilage was decreased dramatically (70 and 50%, respectively) by molybdate. Molybdate did not affect GAG chain elongation, as there was no effect of molybdate on [3H]glucosamine uptake into patella cartilage. These results indicate that molybdate impairs sulfation of GAGs. In an attempt to determine the mechanism of the molybdate-induced decrease in GAG sulfation, the effect of molybdate and sulfate on the incorporation of sulfate into GAGs was examined in vitro using monolayer chondrocyte cultures. Molybdate reduced the sulfation of GAGs in chondrocytes in vitro, but only at concentrations higher than the blood concentration of molybdate given in vivo that decreased GAG sulfation. Molybdate given in vivo decreases plasma sulfate to levels, which when used in vitro, decreases GAG sulfation. Therefore, molybdate treatment decreases sulfate availability and the sulfation of glycosaminoglycans.
Oguro
T
T
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Madhu
C
C
Liu
J
J
Klaassen
C D
CD
D000116:Acetylgalactosamine / Q000378:metabolism*; D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism; D002478:Cells, Cultured; D004187:Disaccharides / Q000032:analysis; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006132:Growth Plate / Q000166:cytology / Q000378:metabolism; D008297:Male; D008982:Molybdenum / Q000633:toxicity*; D010329:Patella; D051381:Rats; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000378:metabolism*
D004187:Disaccharides; D006025:Glycosaminoglycans; D013431:Sulfates; C044659:molybdate; D008982:Molybdenum; D000116:Acetylgalactosamine; D005944:Glucosamine