scholarly journals Gene Therapy for Systemic or Organ Specific Delivery of Manganese Superoxide Dismutase

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1057
Author(s):  
Joel S. Greenberger ◽  
Amitava Mukherjee ◽  
Michael W. Epperly
Keyword(s):  
Gene Therapy ◽  
Superoxide Dismutase ◽  
Radiation Protection ◽  
Mammalian Cells ◽  
Manganese Superoxide Dismutase ◽  
Lessons Learned ◽  
Current Status ◽  
Manganese Superoxide

Manganese superoxide dismutase (MnSOD) is a dominant component of the antioxidant defense system in mammalian cells. Since ionizing irradiation induces profound oxidative stress, it was logical to test the effect of overexpression of MnSOD on radioresistance. This task was accomplished by introduction of a transgene for MnSOD into cells in vitro and into organs in vivo, and both paradigms showed clear radioresistance following overexpression. During the course of development and clinical application of using MnSOD as a radioprotector, several prominent observations were made by Larry Oberley, Joel Greenberger, and Michael Epperly which include (1) mitochondrial localization of either manganese superoxide dismutase or copper/zinc SOD was required to provide optimal radiation protection; (2) the time required for optimal expression was 12–18 h, and while acceptable for radiation protection, the time delay was impractical for radiation mitigation; (3) significant increases in intracellular elevation of MnSOD activity were required for effective radioprotection. Lessons learned during the development of MnSOD gene therapy have provided a strategy for delivery of small molecule SOD mimics, which are faster acting and have shown the potential for both radiation protection and mitigation. The purpose of this review is to summarize the current status of using MnSOD-PL and SOD mimetics as radioprotectors and radiomitigators.

scholarly journals Radioprotection In Vitro and In Vivo by Minicircle Plasmid Carrying the Human Manganese Superoxide Dismutase Transgene

2008 ◽  
Vol 19 (8) ◽  
pp. 820-826 ◽  
Author(s):  
Xichen Zhang ◽  
Michael W. Epperly ◽  
Mark A. Kay ◽  
Zhi-Ying Chen ◽  
Tracy Dixon ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Manganese Superoxide Dismutase ◽  
Manganese Superoxide

Radioprotection In Vitro and In Vivo by Mini Circle Plasmid Containing the Human Manganese Superoxide Dismutase (MnSOD) Transgene

2008 ◽  
Vol 0 (ja) ◽  
pp. 081015093227032
Author(s):  
Xichen Zhang ◽  
Michael W Epperly ◽  
Mark A Kay ◽  
Tracy Smith ◽  
Darcy Franicola ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Manganese Superoxide Dismutase ◽  
Manganese Superoxide

scholarly journals Manganese superoxide dismutase (MnSOD) catalyzes NO-dependent tyrosine residue nitration

2005 ◽  
Vol 70 (4) ◽  
pp. 601-608 ◽  
Author(s):  
Srdjan Stojanovic ◽  
Dragana Stanic ◽  
Milan Nikolic ◽  
Smiljana Raicevic ◽  
Mihajlo Spasic ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Manganese Superoxide Dismutase ◽  
Prolonged Exposure ◽  
In Vitro Study ◽  
Enzyme Inactivation ◽  
Tyrosine Nitration ◽  
Tyrosine Residue ◽  
Manganese Superoxide

The peroxynitrite-induced nitration of manganese superoxide dismutase (MnSOD) tyrosine residue, which causes enzyme inactivation, is well established. This led to suggestions that MnSOD nitration and inactivation in vivo, detected in various diseases associated with oxidative stress and overproduction of nitric monoxide (NO), conditions which favor peroxynitrite formation, is also caused by peroxynitrite. However, our previous in vitro study demonstrated that exposure of MnSOD to NO led to NO conversion into nitrosonium (NO+) and nitroxyl (NO?) species, which caused enzyme modifications and inactivation. Here it is reported that MnSOD is tyrosine nitrated upon exposure to NO, as well as that MnSOD nitration contributes to inactivation of the enzyme. Collectively, these observations provide a compelling argument supporting the generation of nitrating species in MnSOD exposed to NO and shed a new light on MnSOD tyrosine nitration and inactivation in vivo. This may represent a novel mechanism by which MnSOD protects cell from deleterious effects associated with overproduction of NO. However, extensive MnSOD modification and inactivation associated with prolonged exposure to NO will amplify the toxic effects caused by increased cell superoxide and NO levels.

scholarly journals The activity of superoxide-dismutase in animal cell culture CHO-K1 after treatment with fullerenol and mytomicine C

2009 ◽  
Vol 63 (3) ◽  
pp. 143-149 ◽  
Author(s):  
Visnja Bogdanovic ◽  
Marija Slavic ◽  
Jasminka Mrdjanovic ◽  
Slavica Solajic ◽  
Aleksandar Djordjevic
Keyword(s):  
Superoxide Dismutase ◽  
Mammalian Cells ◽  
Animal Cell ◽  
Water Soluble ◽  
Cytotoxic Agents ◽  
Antioxidant Defenses ◽  
Free Radical Scavengers ◽  
Sod Activity

Eukaryotic cell survives in predominantly reduced conditions. Homeostasis of cellular redox system is an imperative of cell surviving and its normal metabolism. ROS are well recognized for playing a dual role as both deleterious and beneficial species, since they can be either harmful or beneficial to living systems. These species are mutagenic compounds known to lead to DNA damage, favor cell transformation, and contribute to the development of a variety of malignant diseases. All the effects of oxidants are influenced by the cellular antioxidant defenses. This multilayer system consists of low molecular weight components and several antioxidant enzymes. Superoxide dismutases (SODs) are the only enzymes dismuting superoxide radicals. Mitomycin C, a cross-linking agent, demonstrated genotoxicity in all in vitro and in vivo test systems in mammalian cells and animals. Water-soluble fullerenes are well known as cytotoxic agents for many cell lines in vitro. At the other side, fullerenols are good free radical scavengers and antioxidants both in vitro and in vivo. This paper investigates the effects of fullerenol on survival and fullerenol/ /mytomicine (MMC) treatment on superoxide-dismutase (SOD) activity in CHO-K1 cells. Samples were treated 3 and 24 h with fullerenol (C60(OH)24) at concentration range 0.01-0.5 mg/mL and survival was monitored with dye exclusion test (DET). The activity of total SOD was estimated in samples treated with chosen concentrations of fullerenol and MMC (0.5 and 0.1 mg/mL) after 3 and 24 h of cell incubation. Increasing of C60(OH)24 concentration leads to decreasing of percent of surviving cells 3 and 24 h after incubation. The activity of total SOD enhanced with higher concentration of fullerenol, while decreased in the highest concentration at both experimental points. In samples treated with MMC, as well as in samples treated with fullerenol (0.0625 mg/mL) + MMC was noticed boost in total SOD activity in comparison with controls. Treatment with fullerenol decreased SOD activity in rest of samples treated with MMC. Decreased activity of superoxide-dismutase in almost all samples treated with fullerenol and MMC might be contributed to antioxidative properties of fullerenol. Increased enzyme level at concentration of 0.0625 mg/mL may be due to its prooxidative activity.

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