Acid and Neutral Sphingomyelinase Behavior in Radiation-Induced Liver Pyroptosis and in the Protective/Preventive Role of rMnSOD
Open Access
- 6 May 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (9), 3281
- https://doi.org/10.3390/ijms21093281
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.Keywords
Funding Information
- Italian Space Agency (“Project RASC,number of contract: 2015-008-R.“Project RASC, number of contract: 2015-008-R)
This publication has 37 references indexed in Scilit:
- Nuclear Lipid Microdomain as Place of Interaction between Sphingomyelin and DNA during Liver RegenerationInternational Journal of Molecular Sciences, 2013
- Emerging inflammasome effector mechanismsNature Reviews Immunology, 2011
- Anterograde and retrograde transport of neutral sphingomyelinase-2 between the Golgi and the plasma membraneBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2010
- Identification and Characterization of Murine Mitochondria-associated Neutral Sphingomyelinase (MA-nSMase), the Mammalian Sphingomyelin Phosphodiesterase 5Published by Elsevier BV ,2010
- A Novel Mitochondrial Sphingomyelinase in Zebrafish CellsPublished by Elsevier BV ,2009
- Bioactive sphingolipids: metabolism and functionJournal of Lipid Research, 2009
- Neutral Sphingomyelinase-3 Is a DNA Damage and Nongenotoxic Stress-Regulated Gene That Is Deregulated in Human MalignanciesMolecular Cancer Research, 2008
- Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic CellsInfection and Immunity, 2005
- Chromatin‐associated sphingomyelin: metabolism in relation to cell functionCell Biochemistry and Function, 2003
- Chromatin sphingomyelin changes in cell proliferation and/or apoptosis induced by ciprofibrateJournal of Cellular Physiology, 2003