title: ERK1/2 are involved in low potassium-induced apoptotic signaling downstream of ASK1-p38 MAPK pathway in cultured cerebellar granule neurons.
abstract: 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.
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Numakawa
authors.forename: Daisaku
authors.initials: D
authors.lastname: Yokomaku
authors.forename: Naoki
authors.initials: N
authors.lastname: Adachi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hatanaka
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamada
authors.forename: Koji
authors.initials: K
authors.lastname: Shimoke
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ikeuchi
mesh_terms: 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*
chemical_list: 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