Premium
P4‐224: Epigenetic control of Aquaporin 1 expression by the amyloid precursor protein
Author(s) -
Huysseune Sandra,
KienlenCampard Pascal,
Hébert Sébastien,
Brion JeanPierre,
Strooper Bart,
Octave JeanNoël
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.690
Subject(s) - amyloid precursor protein , biology , gene , gene expression , presenilin , microbiology and biotechnology , epigenetics , regulation of gene expression , transcription (linguistics) , aquaporin 1 , transcriptional regulation , transcription factor , genetics , alzheimer's disease , medicine , disease , mechanical engineering , linguistics , philosophy , pathology , water channel , engineering , inlet
APP (sAPP) as well as an electrochemiluminescence-based multi-spot ELISA to distinguish between sAPP alpha and sAPP-beta secretion. The intraand extracelluar cleavage fragments were analyzed by Western Blot. Results: The SEAP reporter-assay showed a moderate increase of sAPP in the medium upon APP overexpression in HEK293 and N2A cells and an additional increase when overexpressed together with BACE1, indicating a sAPPbeta increase. This effect was depleted by adding lcLRP. To verify the cleavage product as sAPPbeta, we applied multi-spot ELISA. This ELISA revealed the expected increase of sAPPalpha after transfection with APP. This increase changed to sAPPbeta after BACE1 coexpression. Additional overexpression of lcLRP led to a decrease of both sAPPalpha as well as sAPPbeta in cell culture supernatant. Conclusions: We found a decrease of sAPPalpha as well as sAPPbeta upon lcLRP coexpression supporting our notion of a competition between lcLRP and APP towards the BACE1 cleavage. Our results suggest a complex role of LRP in APP processing besides influencing APP internalization.