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

Abstract

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 microM 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 microM Pb(II) treatment for 24 h caused a discrete stimulation of p38(MAPK) phosphorylation. However, 1 and 10 microM 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 microM 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.

Ubiquitous hazardous metal lead induces TNF-α in human phagocytic THP-1 cells: Primary role of ERK 1/2

“…Despite the suggested role of TNF-␣ in the pathogenesis of various inflammatory disease, the mechanisms by which Pb exposure increases TNF-␣ expression are not well understood. Pb had the capability to modulate the activity of several important signaling molecules including ERK1/2, p38 MAPK and JNK [22][23][24][25]. However, it is not known whether changes induced by Pb in these pathways can modulate TNF-␣ transcription and/or translation in phagocytic cells.…”

Serum c-kit Protein Detection as a Reliable Biomarker for the Diagnosis of Gastrointestinal Stromal Tumors: a Case-Control Study

“…On the contrary, [20] showed that both p38 and JNK were significantly stimulated after treatment with Pb for 48 hours, yet ERK was not modified, they emphasized on the differential stimulation of the MAP kinases in different researches and how it is possibly related to the concentration and time of exposure of Pb. Our exposure time in that case was 5 minutes with a relatively small dose (100 µM) and that might explain in part that discrepancy.…”

“…HaCaTs were seeded for immunocytochemistry onto 0.1% gelatine pre-coated cover slips in 24-multiwell plate. The HaCaT cells were treated with 100 µM Pb [20] in culture medium for 5 minutes or 6 hours, and compared with control (sham-treated with H 2 O as vehicle control).…”

Region-specific alterations of AMPA receptor phosphorylation and signaling pathways in the pilocarpine model of epilepsy

“…For quantification of phosphorylation and immunocontent of the targets, western blot analysis was performed as previously described (Cordova et al, 2004;Figueiredo et al, 2011;Leal et al, 2002;Lopes et al, 2012Lopes et al, , 2013Posser et al, 2007). Animals were euthanized by decapitation and the brains were excised from the skull.…”