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.

Human Mn-superoxide dismutase inactivation by peroxynitrite: a paradigm of metal-catalyzed tyrosine nitration in vitro and in vivo

Metallomics ◽  
2018 ◽  
Vol 10 (5) ◽  
pp. 679-695 ◽  
Author(s):  
Verónica Demicheli ◽  
Diego M. Moreno ◽  
Rafael Radi
Keyword(s):  
Superoxide Dismutase ◽  
Active Site ◽  
Enzyme Inactivation ◽  
Tyrosine Nitration ◽  
Post Translational Modification ◽  
Biologically Relevant ◽  
Metal Catalyzed

Nitration of human MnSOD at active site Tyr34 represents a biologically-relevant oxidative post-translational modification that causes enzyme inactivation.

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 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.

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