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

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...

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Veröffentlicht in:International journal of molecular sciences 2020-05, Vol.21 (9), p.3281
Hauptverfasser: Cataldi, Samuela, Borrelli, Antonella, Ceccarini, Maria Rachele, Nakashidze, Irina, Codini, Michela, Belov, Oleg, Ivanov, Alexander, Krasavin, Eugene, Ferri, Ivana, Conte, Carmela, Patria, Federica Filomena, Beccari, Tommaso, Mancini, Aldo, Curcio, Francesco, Ambesi-Impiombato, Francesco Saverio, Albi, Elisabetta
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container_issue 9
container_start_page 3281
container_title International journal of molecular sciences
container_volume 21
creator Cataldi, Samuela
Borrelli, Antonella
Ceccarini, Maria Rachele
Nakashidze, Irina
Codini, Michela
Belov, Oleg
Ivanov, Alexander
Krasavin, Eugene
Ferri, Ivana
Conte, Carmela
Patria, Federica Filomena
Beccari, Tommaso
Mancini, Aldo
Curcio, Francesco
Ambesi-Impiombato, Francesco Saverio
Albi, Elisabetta
description 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.
doi_str_mv 10.3390/ijms21093281
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central
subjects Animals
Apoptosis
Brain research
Caspase 1 - metabolism
Caspase-1
Cell cycle
Cell death
Cell growth
Cytology
Design of experiments
Endoplasmic reticulum
Environmental conditions
Enzymes
Female
Gene expression
Immunomodulation
Inflammation
Inflammatory response
Ionizing radiation
Labeling
Liver
Liver - drug effects
Liver - metabolism
Liver - radiation effects
Metabolism
Mice
Nuclear research
Pretreatment
Proteins
Pyroptosis
Radiation damage
Radiation effects
Radiation Injuries - drug therapy
Radiation Injuries - metabolism
Radiation-Protective Agents - pharmacology
Radiation-Protective Agents - therapeutic use
Sphingomyelin phosphodiesterase
Sphingomyelin Phosphodiesterase - metabolism
Sphingomyelins - metabolism
Thyroid gland
title Acid and Neutral Sphingomyelinase Behavior in Radiation-Induced Liver Pyroptosis and in the Protective/Preventive Role of rMnSOD
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