u-0126 and Potassium-Deficiency

We have recently reported that the ASK1-p38 MAPK pathway has an important role in the low potassium (LK)-induced apoptosis of cultured cerebellar granule neurons. In the present study, we observed that ERK1/2 were significantly activated 6 h after a change of medium from HK (high potassium) to LK. In addition, U0126, a specific inhibitor of MEKs, remarkably prevented the apoptosis of cultured cerebellar granule neurons. Then, we examined the mechanism underlying the activation of ERK1/2 in the LK-induced apoptotic pathway. The addition of SB203580, an inhibitor of p38 MAPK, suppressed the increase in the phosphorylation of ERK1/2 after the change to LK medium. Furthermore, we found that the expression of a constitutively active mutant of ASK1, an upstream kinase of p38 MAPK, enhanced the phosphorylation of ERK1/2. These results suggest that ERK1/2 play a crucial role in LK-induced apoptosis of cultured cerebellar granule neurons and that the LK-stimulated activation of ERK1/2 is regulated by the ASK1-p38 MAPK pathway.

Topics: Adenoviridae; Animals; Apoptosis; Blotting, Western; Butadienes; Cells, Cultured; Cerebellum; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Female; Immunohistochemistry; Male; MAP Kinase Kinase Kinase 5; Mitogen-Activated Protein Kinase 7; Neurons; Nitriles; p38 Mitogen-Activated Protein Kinases; Potassium Deficiency; Rats; Rats, Wistar; Signal Transduction; Tetrazolium Salts; Thiazoles