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 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.
Verfasserangaben: | Ekaterini Copanaki, Tina Schürmann, Anne EckertORCiDGND, Kristina Leuner, Walter E. MüllerGND, Jochen H. M. PrehnORCiD, Donat KögelORCiD |
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URN: | urn:nbn:de:hebis:30-40977 |
DOI: | https://doi.org/10.1186/1471-2202-8-S1-P26 |
Titel des übergeordneten Werkes (Englisch): | BMC neuroscience |
Verlag: | BioMed Central [u.a.] |
Verlagsort: | London |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Jahr der Fertigstellung: | 2007 |
Jahr der Erstveröffentlichung: | 2007 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 05.04.2007 |
Jahrgang: | 8(Suppl 1) |
Ausgabe / Heft: | P26 |
Seitenzahl: | 1 |
Bemerkung: | © 2007 Copanaki et al; licensee BioMed Central Ltd. |
Bemerkung: | 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 |
Institute: | Medizin / Medizin |
DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Lizenz (Deutsch): | Deutsches Urheberrecht |