Differentiation increases the resistance of neuronal cells to amyloid toxicity.
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.
Cecchi
Cristina
C
Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy. cristina.cecchi@unifi.it
Pensalfini
Anna
A
Liguri
Gianfranco
G
Baglioni
Serena
S
Fiorillo
Claudia
C
Guadagna
Simone
S
Zampagni
Mariagioia
M
Formigli
Lucia
L
Nosi
Daniele
D
Stefani
Massimo
M
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
D000682:Amyloid; D008563:Membrane Lipids; D017382:Reactive Oxygen Species; D002784:Cholesterol; D000252:Calcium-Transporting ATPases; D002118:Calcium