ERK1/2 are involved in low potassium-induced apoptotic signaling downstream of ASK1-p38 MAPK pathway in cultured cerebellar granule neurons.
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.
Yamagishi
Satoru
S
Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Matsumoto
Tomoya
T
Numakawa
Tadahiro
T
Yokomaku
Daisaku
D
Adachi
Naoki
N
Hatanaka
Hiroshi
H
Yamada
Masashi
M
Shimoke
Koji
K
Ikeuchi
Toshihiko
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D048848:MAP Kinase Kinase Kinase 5 / Q000502:physiology*; D008297:Male; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D011191:Potassium Deficiency / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; D013778:Tetrazolium Salts; D013844:Thiazoles; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D048054:Mitogen-Activated Protein Kinase 7; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C022616:thiazolyl blue