ERK1/2 are involved in low potassium-induced apoptotic signaling downstream of ASK1-p38 MAPK pathway in cultured cerebellar granule neurons |
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Authors: | Yamagishi Satoru Matsumoto Tomoya Numakawa Tadahiro Yokomaku Daisaku Adachi Naoki Hatanaka Hiroshi Yamada Masashi Shimoke Koji Ikeuchi Toshihiko |
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Institution: | Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan. |
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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. |
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Keywords: | Development and regeneration Neuronal death |
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