The amyloid precursor protein protects PC12 cells against endoplasmic reticulum stress-induced apoptosis

Kögel, Donat and Schomburg, Robert and Schürmann, Tina and Reimertz, Claus and König, Hans-Georg and Poppe, Monika and Eckert, Anne and Müller, Walter E. and Prehn, Jochen H. M.. (2003) The amyloid precursor protein protects PC12 cells against endoplasmic reticulum stress-induced apoptosis. Journal of neurochemistry, Vol. 87, H. 1. pp. 248-256.

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Official URL: http://edoc.unibas.ch/dok/A5253484

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Endoplasmic reticulum (ER) stress is believed to play an important role in neurodegenerative disorders such as Alzheimer's disease. In the present study, we investigated the effect of the human amyloid precursor protein (APP) on the ER stress response in PC12 cells. Tunicamycin, an inhibitor of N-glycosylation, rapidly induced the expression of the ER-resident chaperone Bip/grp78, a known target gene of the unfolded protein response. Prolonged treatment with tunicamycin (</= 12 h) resulted in the activation of executioner caspases 3 and 7. Interestingly, PC12 cells overexpressing human wild-type APP (APPwt) showed increased resistance to tunicamycin-induced apoptosis compared with empty vector-transfected controls. This neuroprotective effect was significantly diminished in cells expressing the Swedish mutation of APP (KM670/671NL). Similar effects were observed when ER stress was induced with brefeldin A, an inhibitor of ER-to-Golgi protein translocation. Of note, APP-mediated neuroprotection was not associated with altered expression of Bip/grp78 or transcription factor C/EBP homologous protein-10 (CHOP/GADD153), suggesting that APP acted either downstream or independently of ER-to-nucleus signaling. Our data indicate that APP plays an important physiological role in protecting neurons from the consequences of prolonged ER stress, and that APP mutations associated with familial Alzheimer's disease may impair this protective activity.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK
UniBasel Contributors:Eckert, Anne
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:23
Deposited On:22 Mar 2012 13:36

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