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Differentiation Increases the Resistance of Neuronal Cells to Amyloid Toxicity

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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 Aβ1-40, Aβ1-42 and HypF-N prefibrillar aggregate toxicity respect to undifferentiated cells treated similarly. Earlier and sharper increases in cytosolic Ca2+ 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 Ca2+-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.

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Abbreviations

BSA:

Bovine serum albumin

CR:

Congo Red

CM-H2,DCFDA:

2′,7′-Dichlorodihydrofluorescein diacetate, acetyl ester

DCF:

Dichlorofluorescein

DMEM:

Dulbecco’s Modified Eagle’s Medium

DMSO:

Dimethylsulfoxide

ECL:

Enhanced chemiluminescence

FAD:

Familial Alzheimer disease

FBS:

Fetal bovine serum

GAP43:

Growth-associated-protein

HBSS:

Hanks balanced salt solution

HEPES:

N-(2-Hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid)

HRP:

Horseradish peroxidase

HypF-N:

N-Terminal domain of the prokaryotic hydrogenase maturation factor

LDH:

Lactate dehydrogenase

MTP:

Mitochondrial permeability transition pore

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NOS:

NO synthase

PBS:

Phosphate buffered saline

PEG-cholesterol:

Polyoxyetanyl-cholesteryl sebacate

PDTC:

Pyrrolidinedithiocarbamate

PI:

Propidium iodide

PMSF:

Phenylmethylsulphonylfluoride

PS:

Phosphatidylserine

PVDF:

Polyvinylidene difluoride

RA:

Retinoic acid

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SDS-PAGE:

Sodium dodecylsulfate polyacrylamide gel electrophoresis

TFE:

Trifluoroethanol

TM-AFM:

Tapping mode atomic force microscopy

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Acknowledgements

We thank Roberto Caporale for technical advice. This study was supported by grants from the Italian MIUR (project number 2005054147_001 and 2005053998_001) and Compagnia di San Paolo, Torino, Italy (ref. n. 2004.0995).

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Authors and Affiliations

  1. Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy

    Cristina Cecchi, Anna Pensalfini, Gianfranco Liguri, Serena Baglioni, Claudia Fiorillo, Simone Guadagna, Mariagioia Zampagni & Massimo Stefani

  2. Research Centre on the Molecular Basis of Neurodegeneration, University of Florence, 50134, Florence, Italy

    Cristina Cecchi, Gianfranco Liguri & Massimo Stefani

  3. Department of Anatomy, Histology and Forensic Medicine, University of Florence, 50134, Florence, Italy

    Lucia Formigli & Daniele Nosi

Authors
  1. Cristina Cecchi
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  2. Anna Pensalfini
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  3. Gianfranco Liguri
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  4. Serena Baglioni
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  5. Claudia Fiorillo
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  8. Lucia Formigli
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  9. Daniele Nosi
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  10. Massimo Stefani
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Correspondence to Cristina Cecchi.

Additional information

Special issue article in honor of Dr. Anna Maria Giuffrida-Stella.

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Cecchi, C., Pensalfini, A., Liguri, G. et al. Differentiation Increases the Resistance of Neuronal Cells to Amyloid Toxicity. Neurochem Res 33, 2516–2531 (2008). https://doi.org/10.1007/s11064-008-9627-7

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  • DOI: https://doi.org/10.1007/s11064-008-9627-7

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