title: Oligomeric beta-amyloid(1-42) induces the expression of Alzheimer disease-relevant proteins in cholinergic SN56.B5.G4 cells as revealed by proteomic analysis.
abstract: Alzheimer's disease (AD) is characterized by cholinergic dysfunction and progressive basal forebrain cell loss which has been hypothesized to be associated with extensive accumulation of beta-amyloid (Abeta). To reveal whether oligomeric Abeta displays a particular toxicity for cholinergic neurons, the cholinergic cell line SN56.B5.G4 (SN56) was used as a model. Recently performed microarray analyses demonstrated that genes affected by exposure of SN56 cells with 50 microM oligomeric Abeta(1-42) for 24 h were involved in protein modification and degradation [Heinitz, K., Beck, M., Schliebs, R., Perez-Polo, J.R., 2006. Toxicity mediated by soluble oligomers of beta-amyloid(1-42) on cholinergic SN56.B5.G4 cells. J. Neurochem. 98, 1930-1945]. Using a proteomic approach, we compared the levels of proteins and specially of phosphorylated proteins in cytosolic fractions of cell lysates from cholinergic SN56 cells exposed to 50 microM Abeta(1-42) for 24h to those in control incubations. We show here that the levels of calreticulin, and mitogen-activated protein kinase (MAPK) kinase 6c were up-regulated in cholinergic SN56 cells exposed to Abeta(1-42), while gamma-actin appeared down-regulated. Abeta(1-42) exposure of cholinergic SN56 cells led to decreased phosphorylation of phosphoproteins, such as the Rho GDP dissociation inhibitor, the ubiquitin carboxyl terminal hydrolase-1, and the tubulin alpha-chain isotype Malpha6, as compared to untreated control lysates. The proteins identified have also been reported to be affected in brains of AD patients, suggesting a potential role of Abeta in influencing the integrity and functioning of the proteome in AD.
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Joerchel
authors.forename: Maik
authors.initials: M
authors.lastname: Raap
authors.forename: Marina
authors.initials: M
authors.lastname: Bigl
authors.forename: Klaus
authors.initials: K
authors.lastname: Eschrich
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schliebs
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D037282:Calreticulin / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D048669:MAP Kinase Kinase 6 / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D020543:Proteome / Q000187:drug effects / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D012686:Septal Nuclei / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D037282:Calreticulin; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D020543:Proteome; C075222:amyloid beta-protein (1-42); D048669:MAP Kinase Kinase 6