Neutral Sphingomyelinase Modulation in the Protective/Preventive Role of rMnSOD from Radiation-Induced Damage in the Brain
Authors: Carmela Conte
Alexander Ivanov
Samuela Cataldi
Maria Rachele Ceccarini
Elisabetta Albi
Federica Filomena Patria
Francesco Saverio Ambesi-Impiombato
Francesco Curcio
Giovanna Traina
Oleg Belov
Ivana Ferri
Irina Nakashidze
Tommaso Beccari
Antonella Borrelli
Eugene Krasavin
Aldo Mancini
Michela Codini
Journal: International journal of molecular sciences (2019)
Discipline: CHEMISTRY
Keywords: brain; cell signaling; neutral sphingomyelinase; pathology; radiation
Affiliations: Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy. ., Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", 80131 Napoli, Italy. ., Laboratory of Radiation Biology, Joint Institute for Nuclear Research, 141980 Dubna, Russia. ., Division of Pathological Anatomy and Histology, Department of Experimental Medicine, School of Medicine and Surgery, University of Perugia, 06126 Perugia, Italy. ., Laedhexa Biotechnologies Inc., San Francisco, CA QB3@953, USA. ., Dipartimento di Area Medica, University of Udine, 33100 Udine, Italy. .

Abstract:  Studies on the relationship between reactive oxygen species (ROS)/manganese superoxide dismutase (MnSOD) and sphingomyelinase (SMase) are controversial. It has been demonstrated that SMase increases the intracellular ROS level and induces gene expression for MnSOD protein. On the other hand, some authors showed that ROS modulate the activation of SMase. The human recombinant manganese superoxide dismutase (rMnSOD) exerting a radioprotective effect on normal cells, qualifies as a possible pharmaceutical tool to prevent and/or cure damages derived from accidental exposure to ionizing radiation. This study aimed to identify neutral SMase (nSMase) as novel molecule connecting rMnSOD to its radiation protective effects. We used a new, and to this date, unique, experimental model to assess the effect of both radiation and rMnSOD in the brain of mice, within a collaborative project among Italian research groups and the Joint Institute for Nuclear Research, Dubna (Russia). Mice were exposed to a set of minor γ radiation and neutrons and a spectrum of neutrons, simulating the radiation levels to which cosmonauts will be exposed during deep-space, long-term missions. Groups of mice were treated or not-treated (controls) with daily subcutaneous injections of rMnSOD during a period of 10 days. An additional group of mice was also pretreated with rMnSOD for three days before irradiation, as a model for preventive measures. We demonstrate that rMnSOD significantly protects the midbrain cells from radiation-induced damage, inducing a strong upregulation of nSMase gene and protein expression. Pretreatment with rMnSOD before irradiation protects the brain with a value of very high nSMase activity, indicating that high levels of activity might be sufficient to exert the rMnSOD preventive role. In conclusion, the protective effect of rMnSOD from radiation-induced brain damage may require nSMase enzyme. 

Retracted: No

PubPeer comments:
 ![file] Figure 1. CTR panel seems a crop of panel 0.5 Gy+rMnSOD ![file] Figure 2. Tubulin. Band 2 (rMnSOD) and band 6 (0.25 Gy+ rMnSOD) seem duplicated. Same for band 3 (0.25Gy) and band 7 (0.5Gy + rMnSOD) ,