2003年2月
Involvement of c-Jun N-terminal kinase in amyloid precursor protein-mediated neuronal cell death
JOURNAL OF NEUROCHEMISTRY
- 巻
- 84
- 号
- 4
- 開始ページ
- 864
- 終了ページ
- 877
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1046/j.0022-3042.2003.01585.x
- 出版者・発行元
- BLACKWELL PUBLISHING LTD
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 Galpha(o) , but not that of Galpha(i) , 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 G(o) .
- リンク情報
-
- DOI
- https://doi.org/10.1046/j.0022-3042.2003.01585.x
- CiNii Articles
- http://ci.nii.ac.jp/naid/80015838575
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/12562529
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000180742400023&DestApp=WOS_CPL
- ID情報
-
- DOI : 10.1046/j.0022-3042.2003.01585.x
- ISSN : 0022-3042
- CiNii Articles ID : 80015838575
- PubMed ID : 12562529
- Web of Science ID : WOS:000180742400023