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

Alessio Crestini, Rosa Vona, Maria Lo Giudice, Marco Sbriccoli, Paola Piscopo, Antonella Borrelli, Roberto Rivabene, Laura Ricceri, Aldo Mancini, Annamaria Confaloni

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)400-411
Number of pages12
JournalNeurochemical Research
Volume44
Issue number2
DOIs
Publication statusPublished - Feb 2019

Keywords

  • Antioxidants/pharmacology
  • Catalase/metabolism
  • Cell Differentiation/drug effects
  • Humans
  • Hydrogen Peroxide/pharmacology
  • Neurons/drug effects
  • Oxidative Stress/drug effects
  • Protein Isoforms/metabolism
  • Reactive Oxygen Species/metabolism
  • Recombinant Proteins/metabolism
  • Superoxide Dismutase/drug effects

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