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 IGF-I induced by zinc deficiency are not understood. We showed that zinc chelation by DTPA (diethylenetriaminepenta-acetic acid) inhibits [3H]thymidine incorporation stimulated by IGF-I in Rat-1 fibroblasts. This inhibition was specific of zinc chelation since it was prevented by the addition of zinc to DTPA. The stimulation of MAPK, which is crucial for the [3H]thymidine incorporation induced by IGF-I in Rat-1 cells, was partially blunted by DTPA. Therefore, the inhibition of the mitogenic action of IGF-I in Rat-1 fibroblasts by DTPA is potentially caused by decreased MAPK activation by IGF-I.
Lefebvre
D
D
Diabetes and Nutrition Unit, Université Catholique de Louvain, Brussels, Belgium.
Boney
C M
CM
Ketelslegers
J M
JM
Thissen
J P
JP
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007553:Isotope Labeling; D004369:Pentetic Acid / Q000494:pharmacology; D051381:Rats; D014316:Tritium; D015032:Zinc / Q000378:metabolism*
D002614:Chelating Agents; D014316:Tritium; D007334:Insulin-Like Growth Factor I; D004369:Pentetic Acid; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D015032:Zinc