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.
Highlights
Sphingomyelins (SMs) are a class of bioactive lipid molecules that act as key modulators of different pathophysiologic processes, including cell growth, cell death, autophagy, stress, inflammatory responses, and cancer [1]
It is activated in response to stress by inducing apoptosis [9] and suppresses hepatocellular carcinoma [10]. nSMase2 is specific to the inner leaflet of the plasma membrane and is involved in many cell responses, such as cell growth arrest, exosome formation, and inflammatory response [11]. nSMase3 is located in the endoplasmic reticulum and is involved in TNF-α mediated signaling, tumorigenesis [6], and cellular stress response [12]
To study what happens to the metabolism of hepatic SM via both the lysosomal and endoplasmic reticulum/nucleus SMase during irradiation, and to ascertain if this process can be modulated by protective molecules, we used the same experimental model previously applied to evaluate the effects of both ionizing radiation and a specific protective molecule in the brain [22]
Summary
Sphingomyelins (SMs) are a class of bioactive lipid molecules that act as key modulators of different pathophysiologic processes, including cell growth, cell death, autophagy, stress, inflammatory responses, and cancer [1]. NSMase is located in the endoplasmic reticulum and is involved in TNF-α mediated signaling, tumorigenesis [6], and cellular stress response [12]. To study what happens to the metabolism of hepatic SM via both the lysosomal and endoplasmic reticulum/nucleus SMase during irradiation, and to ascertain if this process can be modulated by protective molecules, we used the same experimental model previously applied to evaluate the effects of both ionizing radiation and a specific protective molecule in the brain [22]. Since ionizing radiation induces oxidative stress, and rMnSOD has specific antioxidant and anti-free radical activity, in the previous study, we analyzed the behavior of the nSMase that is stimulated in the cellular stress response [12]. Resultsof an observational study of a novel experiment that could be useful to the scientific community as the basis for future work
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