Inhibition of insulin-like growth factor-I mitogenic action by zinc chelation is associated with a decreased mitogen-activated protein kinase activation in RAT-1 fibroblasts

The mechanisms responsible for the resistance to the anabolic actions of IG F-I induced by zinc deficiency are not understood. We showed that zinc chel ation by DTPA (diethylenetriaminepenta-acetic acid) inhibits [H-3]thymidine incorporation stimulated by IGF-I in Rat-1 fibroblasts, This inhibition wa s specific of zinc chelation since it was prevented by the addition of zinc to DTPA. The stimulation of MAPK, which is crucial for the [H-3]thymidine incorporation induced by IGF-I in Rat-1 cells, was partially blunted by DTP A, Therefore, the inhibition of the mitogenic action of IGF-I in Rat-1 fibr oblasts by DTPA is potentially caused by decreased MAPK activation by IGF-I . (C) 1999 Federation of European Biochemical Societies.