Neutral sphingomyelinase modulation in the protective/preventive role of rMnSOD from radiation-induced damage in the brain

Samuela Cataldi, Antonella Borrelli, Maria Rachele Ceccarini, Irina Nakashidze, Michela Codini, Oleg Belov, Alexander Ivanov, Eugene Krasavin, Ivana Ferri, Carmela Conte, Federica Filomena Patria, Giovanna Traina, Tommaso Beccari, Aldo Mancini, Francesco Curcio, Francesco Saverio Ambesi-Impiombato, Elisabetta Albi

Research output: Contribution to journalArticle

Abstract

Studies on the relationship between reactive oxygen species (ROS)/manganese superoxide dismutase (MnSOD) and sphingomyelinase (SMase) are controversial. It has been demonstrated that SMase increases the intracellular ROS level and induces gene expression for MnSOD protein. On the other hand, some authors showed that ROS modulate the activation of SMase. The human recombinant manganese superoxide dismutase (rMnSOD) exerting a radioprotective effect on normal cells, qualifies as a possible pharmaceutical tool to prevent and/or cure damages derived from accidental exposure to ionizing radiation. This study aimed to identify neutral SMase (nSMase) as novel molecule connecting rMnSOD to its radiation protective effects. We used a new, and to this date, unique, experimental model to assess the effect of both radiation and rMnSOD in the brain of mice, within a collaborative project among Italian research groups and the Joint Institute for Nuclear Research, Dubna (Russia). Mice were exposed to a set of minor γ radiation and neutrons and a spectrum of neutrons, simulating the radiation levels to which cosmonauts will be exposed during deep-space, long-term missions. Groups of mice were treated or not-treated (controls) with daily subcutaneous injections of rMnSOD during a period of 10 days. An additional group of mice was also pretreated with rMnSOD for three days before irradiation, as a model for preventive measures. We demonstrate that rMnSOD significantly protects the midbrain cells from radiation-induced damage, inducing a strong upregulation of nSMase gene and protein expression. Pretreatment with rMnSOD before irradiation protects the brain with a value of very high nSMase activity, indicating that high levels of activity might be sufficient to exert the rMnSOD preventive role. In conclusion, the protective effect of rMnSOD from radiation-induced brain damage may require nSMase enzyme.

Original languageEnglish
Article number5431
JournalInternational Journal of Molecular Sciences
Volume20
Issue number21
DOIs
Publication statusPublished - Nov 1 2019

Keywords

  • Brain
  • Cell signaling
  • Neutral sphingomyelinase
  • Pathology
  • Radiation
  • Sphingomyelin metabolism

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Cataldi, S., Borrelli, A., Ceccarini, M. R., Nakashidze, I., Codini, M., Belov, O., Ivanov, A., Krasavin, E., Ferri, I., Conte, C., Patria, F. F., Traina, G., Beccari, T., Mancini, A., Curcio, F., Ambesi-Impiombato, F. S., & Albi, E. (2019). Neutral sphingomyelinase modulation in the protective/preventive role of rMnSOD from radiation-induced damage in the brain. International Journal of Molecular Sciences, 20(21), [5431]. https://doi.org/10.3390/ijms20215431