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Differentiation-Dependent Effects of a New Recombinant Manganese Superoxide Dismutase on Human SK-N-BE Neuron-Like Cells

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Abstract

We have recently isolated a new isoform of recombinant manganese superoxide dismutase (rMnSOD) which provides a potent antitumor activity and strongly counteracts the occurrence of oxidative stress and tissue inflammation. This isoform, in addition to the enzymatic action common to all SODs, also shows special functional and structural properties, essentially due to the presence of a first leader peptide that allows the protein to enter easily into cells. Among endogenous antioxidants, SOD constitutes the first line of natural defence against pathological effects induced by an excess of free radicals. Here, we firstly describe the effects of our rMnSOD administration on the proliferant and malignant undifferentiated human neuroblastoma SK-N-BE cell line. Moreover, we also test the effects of rMnSOD in the all trans retinoic-differentiated SK-N-BE neuron-like cells, a quiescent “not malignant” model. While rMnSOD showed an antitumor activity on proliferating cells, a poor sensitivity to rMnSOD overload in retinoid-differentiated neuron-like cells was observed. However, in the latter case, in presence of experimental-induced oxidative stress, overcharge of rMnSOD enhanced the oxidant effects, through an increase of H2O2 due to low activity of both catalase and glutathione peroxidase. In conclusion, our data show that rMnSOD treatment exerts differential effects, which depend upon both cell differentiation and redox balance, addressing attention to the potential use of the recombinant enzyme on differentiated neurons. These facts ultimately pave the way for further preclinical studies aimed at evaluation of rMnSOD effects in models of neurodegenerative diseases.

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Abbreviations

ATRA:

All-trans retinoic acid

Aβ:

Beta-amyloid peptide

CAT:

Catalase

Cy:

Cyanine

DHE:

Dihydroethidium

Glu:

Glutamic acid

GSH-px:

Glutathione peroxidase

MQ:

Menadione quinone

MTT:

3-[3,4-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

ROS:

Reactive oxygen species

rMnSOD :

Recombinant manganese superoxide dismutase

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Acknowledgements

This work was partially supported by Lega Italiana (Na) per la Lotta Contro i Tumori (LILT). Authors thank Mirko Morrone for its technical help to the experimental activity.

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Authors and Affiliations

  1. Department of Neuroscience, Italian National Institute of Health, Rome, Italy

    Alessio Crestini, Maria Lo Giudice, Marco Sbriccoli, Paola Piscopo, Roberto Rivabene & Annamaria Confaloni

  2. Biomarkers Unit, Center for Gender-Specific Medicine, Italian National Institute of Health, Rome, Italy

    Rosa Vona

  3. Molecular Biology and Viral Oncology Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, “Fondazione G. Pascale”, IRCCS, Naples, Italy

    Antonella Borrelli

  4. Centre for Behavioural Sciences and Mental Health, Italian National Institute of Health, Rome, Italy

    Laura Ricceri

  5. Leadhexa Biotechnologies Inc., San Francisco, CA, USA

    Aldo Mancini

Authors
  1. Alessio Crestini
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  2. Rosa Vona
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  3. Maria Lo Giudice
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  10. Annamaria Confaloni
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Contributions

AC designed and performed experiments, analyzed data and wrote the manuscript; MLG, MS and RR performed experiments; RV, LR and PP contributed to the interpretation of results and made manuscript revisions; AB and AM provided essential materials; AmC conceived the study and wrote the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Annamaria Confaloni.

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Conflict of interest

AM is the founder of Laedhexa Biotechnologies Inc. The others authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Crestini, A., Vona, R., Lo Giudice, M. et al. Differentiation-Dependent Effects of a New Recombinant Manganese Superoxide Dismutase on Human SK-N-BE Neuron-Like Cells. Neurochem Res 44, 400–411 (2019). https://doi.org/10.1007/s11064-018-2686-5

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  • DOI: https://doi.org/10.1007/s11064-018-2686-5

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