scholarly journals Neutral Sphingomyelinase Modulation in the Protective/Preventive Role of rMnSOD from Radiation-Induced Damage in the Brain

2019 ◽  
Vol 20 (21) ◽  
pp. 5431 ◽  
Author(s):  
Samuela Cataldi ◽  
Antonella Borrelli ◽  
Maria Rachele Ceccarini ◽  
Irina Nakashidze ◽  
Michela Codini ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Manganese Superoxide Dismutase ◽  
Nuclear Research ◽  
Protective Effects ◽  
Manganese Superoxide ◽  
Additional Group ◽  
Gene And Protein Expression ◽  
Radiation Induced ◽  
The Brain ◽  
Preventive Role

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.

Prevention of Radiation-Induced Oral Cavity Mucositis by Plasmid/Liposome Delivery of the Human Manganese Superoxide Dismutase (SOD2) Transgene

2003 ◽  
Vol 159 (3) ◽  
pp. 361-370 ◽  
Author(s):  
Hongliang Guo ◽  
Jose A. Seixas-Silva ◽  
Michael W. Epperly ◽  
Joan E. Gretton ◽  
Dong M. Shin ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Oral Cavity ◽  
Manganese Superoxide Dismutase ◽  
Manganese Superoxide ◽  
Radiation Induced

scholarly journals Cardiac Electrophysiological Alterations in Heart/Muscle-Specific Manganese-Superoxide Dismutase-Deficient Mice: Prevention by a Dietary Antioxidant Polyphenol

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Tadahiro Sunagawa ◽  
Takahiko Shimizu ◽  
Akio Matsumoto ◽  
Motoyuki Tagashira ◽  
Tomomasa Kanda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Action Potential ◽  
Heart Muscle ◽  
Chronic Exposure ◽  
Manganese Superoxide Dismutase ◽  
Left Ventricular ◽  
Protective Effects ◽  
Manganese Superoxide ◽  
Dietary Antioxidant

Cardiac electrophysiological alterations induced by chronic exposure to reactive oxygen species and protective effects of dietary antioxidant have not been thoroughly examined. We recorded surface electrocardiograms (ECG) and evaluated cellular electrophysiological abnormalities in enzymatically-dissociated left ventricular (LV) myocytes in heart/muscle-specific manganese-superoxide dismutase-deficient (H/M-Sod2−/−) mice, which exhibit dilated cardiomyopathy due to increased oxidative stress. We also investigated the influences of intake of apple polyphenols (AP) containing mainly procyanidins with potent antioxidant activity. The QRS and QT intervals of ECG recorded in H/M-Sod2−/−mice were prolonged. The effective refractory period in the LV myocardium of H/M-Sod2−/−mice was prolonged, and susceptibility to ventricular tachycardia or fibrillation induced by rapid ventricular pacing was increased. Action potential duration in H/M-Sod2−/−LV myocytes was prolonged, and automaticity was enhanced. The density of the inwardly rectifier K+current (IK1) was decreased in the LV cells of H/M-Sod2−/−mice. The AP intake partially improved these electrophysiological alterations and extended the lifespan in H/M-Sod2−/−mice. Thus, chronic exposure of the heart to oxidative stress produces a variety of electrophysiological abnormalities, increased susceptibility to ventricular arrhythmias, and action potential changes associated with the reduced density ofIK1. Dietary intake of antioxidant nutrients may prevent oxidative stress-induced electrophysiological disturbances.

scholarly journals A Gel Formulation Containing a New Recombinant Form of Manganese Superoxide Dismutase: A Clinical Experience Based on Compassionate Use-Safety of a Case Report

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Lucia Grumetto ◽  
Antonio Del Prete ◽  
Giovanni Ortosecco ◽  
Antonella Borrelli ◽  
Salvatore Del Prete ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Case Report ◽  
Manganese Superoxide Dismutase ◽  
Recombinant Form ◽  
Term Therapy ◽  
Protective Effects ◽  
Manganese Superoxide ◽  
Gel Preparation ◽  
The Right ◽  
Long Term Therapy

Background. We report a case of bilateral posterior subcapsular cataracts (PSCs) in a 24-year-old man with an allergic conjunctivitis history caused by a long-term therapy with glucocorticoids.Case Presentation. The patient showed a visual acuity of 9/10 for both eyes. He followed a therapy with ketotifen and bilastine for four years. During the last six months before our evaluation, he was treated with chloramphenicol and betamethasone, interrupted for onset of cataracts and increased intraocular pressure. We treated him with ophthalmic gel preparation containing a new recombinant form of manganese superoxide dismutase (rMnSOD) at a concentration of 12.5 μg/mL, only for the right eye, while left eye was treated with standard protocol of Bendazac-lysine g 0.5.Conclusion. This case report shows the protective effects of rMnSOD versus PSC disease, probably due to the capacity of rMnSOD of countering free radical species.

scholarly journals Manganese Superoxide Dismutase-Mediated Gene Expression in Radiation-Induced Adaptive Responses

2003 ◽  
Vol 23 (7) ◽  
pp. 2362-2378 ◽  
Author(s):  
Guozheng Guo ◽  
Yan Yan-Sanders ◽  
Beverly D. Lyn-Cook ◽  
Tieli Wang ◽  
Daniel Tamae ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Stress Responses ◽  
Manganese Superoxide Dismutase ◽  
Cyclin A ◽  
Cyclin B1 ◽  
Adaptive Responses ◽  
Human Carcinoma ◽  
Manganese Superoxide ◽  
Radiation Induced ◽  
Mcf 7

ABSTRACT Antioxidant enzymes are critical in oxidative stress responses. Radioresistant variants isolated from MCF-7 human carcinoma cells following fractionated ionizing radiation (MCF+FIR cells) or overexpression of manganese superoxide dismutase (MCF+SOD cells) demonstrated dose-modifying factors at 10% isosurvival of 1.8 and 2.3, respectively. MCF+FIR and MCF-7 cells (exposed to single-dose radiation) demonstrated 5- to 10-fold increases in MnSOD activity, mRNA, and immunoreactive protein. Radioresistance in MCF+FIR and MCF+SOD cells was reduced following expression of antisense MnSOD. DNA microarray analysis and immunoblotting identified p21, Myc, 14-3-3 zeta, cyclin A, cyclin B1, and GADD153 as genes constitutively overexpressed (2- to 10-fold) in both MCF+FIR and MCF+SOD cells. Radiation-induced expression of these six genes was suppressed in fibroblasts from Sod2 knockout mice (−/−) as well as in MCF+FIR and MCF+SOD cells expressing antisense MnSOD. Inhibiting NF-κB transcriptional activity in MCF+FIR cells, by using mutant IκBα, inhibited radioresistance as well as reducing steady-state levels of MnSOD, 14-3-3 zeta, GADD153, cyclin A, and cyclin B1 mRNA. In contrast, mutant IκBα was unable to inhibit radioresistance or reduce 14-3-3 zeta, GADD153, cyclin A, and cyclin B1 mRNAs in MCF+SOD cells, where MnSOD overexpression was independent of NF-κB. These results support the hypothesis that NF-κB is capable of regulating the expression of MnSOD, which in turn is capable of increasing the expression of genes that participate in radiation-induced adaptive responses.

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