title: Differentiation increases the resistance of neuronal cells to amyloid toxicity.
abstract: A substantial lack of information is recognized on the features underlying the variable susceptibility to amyloid aggregate toxicity of cells with different phenotypes. Recently, we showed that different cell types are variously affected by early aggregates of a prokaryotic hydrogenase domain (HypF-N). In the present study we investigated whether differentiation affects cell susceptibility to amyloid injury using a human neurotypic SH-SY5Y cell differentiation model. We found that retinoic acid-differentiated cells were significantly more resistant against Abeta1-40, Abeta1-42 and HypF-N prefibrillar aggregate toxicity respect to undifferentiated cells treated similarly. Earlier and sharper increases in cytosolic Ca(2+) and ROS with marked lipid peroxidation and mitochondrial dysfunction were also detected in exposed undifferentiated cells resulting in apoptosis activation. The reduced vulnerability of differentiated cells matched a more efficient Ca(2+)-ATPase equipment and a higher total antioxidant capacity. Finally, increasing the content of membrane cholesterol resulted in a remarkable reduction of vulnerability and ability to bind the aggregates in either undifferentiated and differentiated cells.
authors.affiliation: Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy. cristina.cecchi@unifi.it
authors.forename: Cristina
authors.initials: C
authors.lastname: Cecchi
authors.forename: Anna
authors.initials: A
authors.lastname: Pensalfini
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Liguri
authors.forename: Serena
authors.initials: S
authors.lastname: Baglioni
authors.forename: Claudia
authors.initials: C
authors.lastname: Fiorillo
authors.forename: Simone
authors.initials: S
authors.lastname: Guadagna
authors.forename: Mariagioia
authors.initials: M
authors.lastname: Zampagni
authors.forename: Lucia
authors.initials: L
authors.lastname: Formigli
authors.forename: Daniele
authors.initials: D
authors.lastname: Nosi
authors.forename: Massimo
authors.initials: M
authors.lastname: Stefani
mesh_terms: D000682:Amyloid / Q000502:physiology*; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000682:Amyloid; D008563:Membrane Lipids; D017382:Reactive Oxygen Species; D002784:Cholesterol; D000252:Calcium-Transporting ATPases; D002118:Calcium