Due to its cytoprotective effects, overexpression of SOD2 has been linked to increased invasiveness of tumormetastasis.
Mutations in this gene have been associated with idiopathiccardiomyopathy (IDC), sporadic motor neuron disease, and cancer. A common polymorphism associated with greater susceptibility to various pathologies is found in the mitochondrial leader targeting sequence (Val9Ala). Mice lacking Sod2 die shortly after birth, indicating that unchecked levels of superoxide are incompatible with mammalian life. However, mice 50% deficient in Sod2 have a normal lifespan and minimal phenotypic defects but do suffer increased DNA damage and increased incidence of cancer. In Drosophila melanogaster, over-expression of Sod2 has been show to increase lifespan by 20%
When animals are exercised at a relatively high work rate, many exercise training studies report that exercise training promotes an increase in myocardial MnSOD activity. This is significant because two recent studies reveal that increased MnSOD activity is essential to achieve optimal training-induced protection against both ischemia/reperfusion(IR)-induced cardiac arrhythmias and infarction. Specifically, using an antisense oligonucleotide against MnSOD to prevent ExTr-induced increases in myocardial MnSOD activity, Yamashita et al. demonstrated that an increase in myocardial MnSOD activity is required to provide training-induced protection against IR-induced myocardial infarction. Similarly, Hamilton et al. , using a MnSOD gene silencing approach, reported that prevention of the ExTr-induced increase in myocardial MnSOD resulted in a loss of training-induced protection against IR-mediated arrhythmias. In contrast to these findings, training-induced increases in cardiac MnSOD are not required to achieve training-induced cardioprotection against myocardial stunning. (Power et al. 2007)
^ abcPias EK, Ekshyyan OY, Rhoads CA, Fuseler J, Harrison L, Aw TY (Apr 2003). "Differential effects of superoxide dismutase isoform expression on hydroperoxide-induced apoptosis in PC-12 cells". The Journal of Biological Chemistry278 (15): 13294–301. doi:10.1074/jbc.M208670200. PMID12551919.
^Van Remmen H, Ikeno Y, Hamilton M, Pahlavani M, Wolf N, Thorpe SR, Alderson NL, Baynes JW, Epstein CJ, Huang TT, Nelson J, Strong R, Richardson A (Dec 2003). "Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging". Physiological Genomics16 (1): 29–37. doi:10.1152/physiolgenomics.00122.2003. PMID14679299.
1ap5: TYR34->PHE MUTANT OF HUMAN MITOCHONDRIAL MANGANESE SUPEROXIDE DISMUTASE
1ap6: TYR34->PHE MUTANT OF HUMAN MITOCHONDRIAL MANGANESE SUPEROXIDE DISMUTASE
1em1: X-RAY CRYSTAL STRUCTURE FOR HUMAN MANGANESE SUPEROXIDE DISMUTASE, Q143A
1ja8: Kinetic Analysis of Product Inhibition in Human Manganese Superoxide Dismutase
1luv: CATALYTIC AND STRUCTURAL EFFECTS OF AMINO-ACID SUBSTITUTION AT HIS 30 IN HUMAN MANGANESE SUPEROXIDE DISMUTASE: INSERTION OF VAL CGAMMA INTO THE SUBSTRATE ACCESS CHANNEL
1luw: CATALYTIC AND STRUCTURAL EFFECTS OF AMINO-ACID SUBSTITUTION AT HIS 30 IN HUMAN MANGANESE SUPEROXIDE DISMUTASE: INSERTION OF VAL CGAMMA INTO THE SUBSTRATE ACCESS CHANNEL
1msd: COMPARISON OF THE CRYSTAL STRUCTURES OF GENETICALLY ENGINEERED HUMAN MANGANESE SUPEROXIDE DISMUTASE AND MANGANESE SUPEROXIDE DISMUTASE FROM THERMUS THERMOPHILUS. DIFFERENCES IN DIMER-DIMER INTERACTIONS.
1n0j: The Structure of Human Mitochondrial MN3+ Superoxide Dismutase Reveals a Novel Tetrameric Interface of Two 4-Helix Bundles
1n0n: Catalytic and Structural Effects of Amino-Acid Substitution at His30 in Human Manganese Superoxide Dismutase
1pl4: Crystal Structure of human MnSOD Y166F mutant
1pm9: CRYSTAL STRUCTURE OF HUMAN MNSOD H30N, Y166F MUTANT
1qnm: HUMAN MANGANESE SUPEROXIDE DISMUTASE MUTANT Q143N
1szx: Role Of Hydrogen Bonding In The Active Site Of Human Manganese Superoxide Dismutase
1var: MITOCHONDRIAL MANGANESE SUPEROXIDE DISMUTASE VARIANT WITH ILE 58 REPLACED BY THR
1xdc: Hydrogen Bonding in Human Manganese Superoxide Dismutase containing 3-Fluorotyrosine
1xil: HYDROGEN BONDING IN HUMAN MANGANESE SUPEROXIDE DISMUTASE CONTAINING 3-FLUOROTYROSINE
1zsp: Contribution to Structure and Catalysis of Tyrosine 34 in Human Manganese Superoxide Dismutase
1zte: Contribution to Structure and Catalysis of Tyrosine 34 in Human Manganese Suerpoxide Dismutase
1zuq: Contribution to Structure and Catalysis of Tyrosine 34 in Human Manganese Superoxide Dismutase
2adp: Nitrated Human Manganese Superoxide Dismutase
2adq: Human Manganese Superoxide Dismutase
2gds: Interrupting the Hydrogen Bonding Network at the Active Site of Human Manganese Superoxide Dismutase
2p4k: Contribution to Structure and Catalysis of Tyrosine 34 in Human Manganese Superoxide Dismutase