Exposure of C6 glioma cells to Pb(II) increases the phosphorylation of p38MAPK and JNK1/2 but not of ERK1/2

Pb(II) is a neurotoxic pollutant that produces permanent cognitive deficits in children. Pb(II) can modulate cell signaling pathways and cell viability in a variety of cell types. However, these actions are not well demonstrated on glial cells, which represent an important target for metals into the central nervous system. The present work was undertaken to determine the ability of Pb(II) in modulating the activity of mitogen activated protein kinases (MAPKs) in cultures of C6 rat glioma cells, a useful functional model for the study of astrocytes. Additionally, cell viability was analyzed by measurement of MTT reduction. Cells were exposed to lead acetate 0.1, 1, 10 mu M for 24 and 48 h. MAPKs activation-in particular ERK1/2, p38(MAPK) and JNK1/2-were analyzed by western blotting. Results showed that 10 mu M Pb(II) treatment for 24 h caused a discrete stimulation of p38(MAPK) phosphorylation. However, 1 and 10 mu M Pb(II) treatment for 48 h provoked a significant stimulation in the phosphorylation state of p38(MAPK) and JNK1/2. The phosphorylation state of ERK1/2 was not modified by any Pb(II) treatment. Moreover, data indicate that at 48 h treatment even 1 mu M Pb(II) can be cytotoxic, causing impairment on cell viability. Therefore, depending on a long incubation period, a significant concomitant activation of p38(MAPK) and JNK1/2 by Pb(II) took place in parallel with the impairment of C6 glioma cells viability.