Acid and Neutral Sphingomyelinase Behavior in Radiation-Induced Liver Pyroptosis and in the Protective/Preventive Role of rMnSOD

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

Research output: Contribution to journalArticle

Abstract

Sphingomyelins (SMs) are a class of relevant bioactive molecules that act as key modulators of different cellular processes, such as growth arrest, exosome formation, and the inflammatory response influenced by many environmental conditions, leading to pyroptosis, a form of programmed cell death due to Caspase-1 involvement. To study liver pyroptosis and hepatic SM metabolism via both lysosomal acid SMase (aSMase) and endoplasmic reticulum/nucleus neutral SMase (nSMase) during the exposure of mice to radiation and to ascertain if this process can be modulated by protective molecules, we used an experimental design (previously used by us) to evaluate the effects of both ionizing radiation and a specific protective molecule (rMnSOD) in the brain in collaboration with the Joint Institute for Nuclear Research, Dubna (Russia). As shown by the Caspase-1 immunostaining of the liver sections, the radiation resulted in the loss of the normal cell structure alongside a progressive and dose-dependent increase of the labelling, treatment, and pretreatment with rMnSOD, which had a significant protective effect on the livers. SM metabolic analyses, performed on aSMase and nSMase gene expression, as well as protein content and activity, proved that rMnSOD was able to significantly reduce radiation-induced damage by playing both a protective role via aSMase and a preventive role via nSMase.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume21
Issue number9
DOIs
Publication statusPublished - May 6 2020

Keywords

  • acid sphingomyelinase
  • liver
  • neutral sphingomyelinase
  • radiation
  • SOD

ASJC Scopus subject areas

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

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    Cataldi, S., Borrelli, A., Ceccarini, M. R., Nakashidze, I., Codini, M., Belov, O., Ivanov, A., Krasavin, E., Ferri, I., Conte, C., Patria, F. F., Beccari, T., Mancini, A., Curcio, F., Ambesi-Impiombato, F. S., & Albi, E. (2020). Acid and Neutral Sphingomyelinase Behavior in Radiation-Induced Liver Pyroptosis and in the Protective/Preventive Role of rMnSOD. International Journal of Molecular Sciences, 21(9). https://doi.org/10.3390/ijms21093281