title: Effects of vanadate on tyrosine phosphorylation and the pattern of glycosaminoglycan synthesis in rabbit chondrocytes in culture.
abstract: The present study examined the effects of high doses of vanadate on glycosaminoglycan (GAG) synthesis and tyrosine phosphorylation in rabbit chondrocytes in confluent cultures. Although 6 microM vanadate increased the incorporation of [3H]glucosamine into chondroitin sulfate proteoglycans twofold, 40-60 microM vanadate suppressed this incorporation fourfold. Although 6 microM vanadate had little effect on [3H]glucosamine incorporation into hyaluronate, 40-60 microM vanadate increased this incorporation threefold. Chemical analyses confirmed that the increase in [3H]glucosamine incorporation into hyaluronate and the decrease in the incorporation into chondroitin sulfate proteoglycan correlated with increased hyaluronate content and decreased chondroitin sulfate content in the cell layers of vanadate-transformed cells. Chondrocytes exposed to 40-60 microM vanadate became typically transformed spindlelike cells. Furthermore, vanadate, at 6 and 60 microM, increased the overall level of phosphotyrosine by 8- and 31-fold, respectively, and 60 microM vanadate enhanced phosphorylation of many phosphotyrosine-containing proteins. These observations suggest that vanadate induces transformation-associated changes in the pattern of GAG synthesis when it induces excess phosphorylation on tyrosine in chondrocyte proteins.
authors: Department of Biochemistry, Faculty of Dentistry, Osaka University, Japan.
authors: M K
authors: MK
authors: Owada
authors: M
authors: M
authors: Iwamoto
authors: T
authors: T
authors: Koike
authors: Y
authors: Y
authors: Kato
mesh_terms: D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D004187:Disaccharides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006820:Hyaluronic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D019000:Phosphotyrosine; D011817:Rabbits; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014639:Vanadium / Q000494:pharmacology*
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D004187:Disaccharides; D006025:Glycosaminoglycans; D014639:Vanadium; D019000:Phosphotyrosine; D014443:Tyrosine; D006820:Hyaluronic Acid; D005944:Glucosamine