The amyloid precursor protein potentiates CHOP induction and cell death in response to ER Ca2+ depletion

Poster presentation: Here we investigated the role of the amyloid precursor protein (APP) in regulation of Ca2+ store depletion-induced neural cell death. Ca2+ store depletion from the endoplasmic reticulum (ER) was indu
Poster presentation: Here we investigated the role of the amyloid precursor protein (APP) in regulation of Ca2+ store depletion-induced neural cell death. Ca2+ store depletion from the endoplasmic reticulum (ER) was induced by the SERCA (Sarco/Endoplasmic Reticulum Calcium ATPase) inhibitor thapsigargin which led to a rapid induction of the unfolded protein response (UPR) and a delayed activation of executioner caspases in the cultures. Overexpression of APP potently enhanced cytosolic Ca2+ levels and cell death after ER Ca2+ store depletion in comparison to vector-transfected controls. GeneChipR and RT-PCR analysis revealed that the expression of classical UPR chaperone genes was not altered by overexpression of APP.Interestingly, the induction of the ER stress-responsive pro-apoptotic transcription factor CHOP was significantly upregulated in APP-overexpressing cells in comparison to vectortransfected controls. Chelation of intracellular Ca2+ with BAPTA-AM revealed that enhanced CHOP expression after store depletion occured in a Ca2+-dependent manner in APPoverexpressing cells. Prevention of CHOP induction by BAPTA-AM and by RNA interference was also able to abrogate the potentiating effect of APP on thapsigargin-induced apoptosis. Application of the store-operated channel (SOC)-inhibitors SK F96365 and 2-APB downmodulated APP-triggered potentiation of cytosolic Ca2+ levels and apoptosis after treatment with thapsigargin. Our data demonstrate that APP-mediated regulation of ER Ca2+ homeostasis significantly modulates Ca2+ store depletion-induced cell death in a SOC- and CHOP-dependent manner, but independent of the UPR.
show moreshow less

Download full text files

Export metadata

  • Export Bibtex
  • Export RIS

Additional Services

    Share in Twitter Search Google Scholar
Metadaten
Author:Ekaterini Copanaki, Tina Schürmann, Anne Eckert, Kristina Leuner, Walter E. Müller, Jochen H. M. Prehn, Donat Kögel
URN:urn:nbn:de:hebis:30-40977
DOI:http://dx.doi.org/10.1186/1471-2202-8-S1-P26
Parent Title (English):BMC Neuroscience
Publisher:BioMed Central [u.a.]
Place of publication:London
Document Type:Article
Language:English
Date of Publication (online):2007/04/05
Year of first Publication:2007
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2007/04/05
Volume:8(Suppl 1)
Issue:P26
Pagenumber:1
Note:
© 2007 Copanaki et al; licensee BioMed Central Ltd.
Note:
From Annual Meeting of the Study Group Neurochemistry. International Conference of the Gesellschaft für Biochemie und Molekularbiologie 2006 (GBM 2006): Molecular pathways in health and disease of the nervous system. - Witten, Germany. 28–30 September 2006
HeBIS PPN:33645094X
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License Logo Veröffentlichungsvertrag für Publikationen

$Rev: 11761 $