Lanthanum Induces Extracellular Signal-regulated Kinase Phosphorylation through Different Mechanisms in HeLa Cells and NIH 3T3 Cells

Lanthanum ion (La³⁺) was generally regarded as calcium antagonist and was used as calcium channel blocker. However, its potential biological effects on cells were poorly understood. In the present work, it was found that La³⁺ could induce rapid extracellular signal-regulated kinase (ERK) phosphorylation in both HeLa cells and NIH 3T3 cells, but different mechanisms were involved. At a concentration of 30μM or higher, La³⁺ enters the cells and activates ERK through a mechanism involving calmodulin activation inside the cells, which is similar to the action of intracellular Ca²⁺. However, at lower concentration, free La³⁺ promoted ERK phosphorylation in NIH 3T3 cells outside the cells through an unknown La³⁺ sensing mechanism, while Ca²⁺ exerted much weaker effect. The present results suggested that the biological effects of La³⁺ on cells maybe involve mechanisms beyond calcium antagonist.