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

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Pyroptosis*; Liver/*metabolism ; Radiation Injuries/*metabolism ; Radiation-Protective Agents/*pharmacology ; Sphingomyelin Phosphodiesterase/*metabolism ; Sphingomyelins/*metabolism; Animals ; Caspase 1/metabolism ; Female ; Liver/drug effects ; Liver/radiation effects ; Mice ; Radiation Injuries/drug therapy ; Radiation-Protective Agents/therapeutic use
    • 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.
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    • Grant Information:
      "Project RASC,number of contract: 2015-008-R."Project RASC, number of contract: 2015-008-R Italian Space Agency
    • Contributed Indexing:
      Keywords: SOD; acid sphingomyelinase; liver; neutral sphingomyelinase; radiation
    • Accession Number:
      0 (Radiation-Protective Agents)
      0 (Sphingomyelins)
      EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
      EC 3.4.22.36 (Caspase 1)
    • Publication Date:
      Date Created: 20200510 Date Completed: 20210201 Latest Revision: 20210201
    • Publication Date:
      20221213
    • Accession Number:
      PMC7247354
    • Accession Number:
      10.3390/ijms21093281
    • Accession Number:
      32384654