Antibody-bound amyloid precursor protein upregulates ornithine decarboxylase expression.
Alzheimer's disease is a neurodegenerative disorder characterised by extracellular accumulation of the Abeta peptide, derived from the amyloid precursor protein (APP). The function of APP as a cell surface receptor was examined by ligand-mimicking using an antibody against the APP extracellular domain. Alterations in gene expression evoked by antibody-bound APP were analysed using human pathway-finder gene arrays and the largest change in expression levels was found for ornithine decarboxylase (ODC). These results were confirmed by Western blotting which showed even higher upregulation on the protein level. APP knockdown by RNAi verified that upregulation of ODC was APP-mediated. This APP signalling event did not require gamma-secretase cleavage, as it was independent of the presence of presenilin-1 or -2. The induced ODC expression was rapid and biphasic, resembling growth-factor stimulated signalling events. This study shows that antibody-bound APP leads to altered gene expression that may be relevant to AD.
Nilsson
Tatjana
T
Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum floor 5, 141 86 Stockholm, Sweden. tatjana.nilsson@ki.se
Malkiewicz
Katarzyna
K
Gabrielsson
Maria
M
Folkesson
Ronnie
R
Winblad
Bengt
B
Benedikz
Eirikur
E
D016564:Amyloid beta-Protein Precursor / Q000276:immunology / Q000502:physiology*; D000936:Antigen-Antibody Complex / Q000494:pharmacology; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D053764:Presenilin-1; D053766:Presenilin-2; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D016564:Amyloid beta-Protein Precursor; D000936:Antigen-Antibody Complex; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D009955:Ornithine Decarboxylase