| First Author | Hashimoto Y | Year | 2003 |
| Journal | J Neurochem | Volume | 84 |
| Issue | 4 | Pages | 864-77 |
| PubMed ID | 12562529 | Mgi Jnum | J:81775 |
| Mgi Id | MGI:2449995 | Doi | 10.1046/j.1471-4159.2003.01585.x |
| Citation | Hashimoto Y, et al. (2003) Involvement of c-Jun N-terminal kinase in amyloid precursor protein-mediated neuronal cell death. J Neurochem 84(4):864-77 |
| abstractText | Amyloid precursor protein (APP), the precursor of Abeta, has been shown to function as a cell surface receptor that mediates neuronal cell death by anti-APP antibody. The c-Jun N-terminal kinase (JNK) can mediate various neurotoxic signals, including Abeta neurotoxicity. However, the relationship of APP-mediated neurotoxicity to JNK is not clear, partly because APP cytotoxicity is Abeta independent. Here we examined whether JNK is involved in APP-mediated neuronal cell death and found that: (i) neuronal cell death by antibody-bound APP was inhibited by dominant-negative JNK, JIP-1b and SP600125, the specific inhibitor of JNK, but not by SB203580 or PD98059; (ii) constitutively active (ca) JNK caused neuronal cell death and (iii) the pharmacological profile of caJNK-mediated cell death closely coincided with that of APP-mediated cell death. Pertussis toxin (PTX) suppressed APP-mediated cell death but not caJNK-induced cell death, which was suppressed by Humanin, a newly identified neuroprotective factor which inhibits APP-mediated cytotoxicity. In the presence of PTX, the PTX-resistant mutant of Galphao, but not that of Galphai, recovered the cytotoxic action of APP. These findings demonstrate that JNK is involved in APP-mediated neuronal cell death as a downstream signal transducer of Go. |
