Tyrosine phosphorylation and morphological transformation induced by four vanadium compounds on MC3T3E1 cells

The present study was performed to determine the phosphotyrosine-protein le vels induced by insulin and by four vanadium derivatives in MC3T3E1 osteobl ast-like cells. We have also attempted to associate these patterns with the vanadium-induced growth and morphological changes of such cells. Vanadate (Vi), vanadyl (VO), bis(maltolato)oxovanadium (IV) (BMOV) and bis( maltolat o)dioxovanadium (V) (BMV) stimulate cell growth in a narrow range of concen tration, but are also inhibitors for the cells at high concentrations. Vana dium-treated cells displayed clear changes in their morphology after overni ght incubation. However, BMV was the least cytotoxic and the weakest induce r of morphological changes. All the compounds promote the phosphorylation o f tyrosine residues in several proteins. This effect was more pronounced at low than at high doses. At low doses (10 mu M), BMV showed a phosphorylati on pattern similar to that of insulin, while Vi, VO and BMOV induced strong phosphorylation of cell proteins. The present findings suggest that the va nadium-induced growth regulation and morphological changes in MC3T3E1 osteo blast-like cells are associated with the ability of these agents to increas e the phosphotyrosine protein levels and to inhibit phosphotyrosine phospha tases. These properties are dependent on the oxidation state as well as on the organic ligand which coordinates the vanadium atom.