Effects of vanadate on tyrosine phosphorylation and the pattern of glycosaminoglycan synthesis in rabbit chondrocytes in culture |
| |
Authors: | M K Owada M Iwamoto T Koike Y Kato |
| |
Institution: | Department of Biochemistry, Faculty of Dentistry, Osaka University, Japan. |
| |
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. |
| |
Keywords: | |
|
|