SOD2

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Superoxide dismutase 2, mitochondrial
Protein SOD2 PDB 1ap5.png
PDB rendering based on 1ap5.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SOD2 ; IPOB; MNSOD; MVCD6
External IDs OMIM147460 MGI98352 HomoloGene530 GeneCards: SOD2 Gene
EC number 1.15.1.1
RNA expression pattern
PBB GE SOD2 215223 s at tn.png
PBB GE SOD2 216841 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 6648 20656
Ensembl ENSG00000112096 ENSMUSG00000006818
UniProt P04179 P09671
RefSeq (mRNA) NM_000636 NM_013671
RefSeq (protein) NP_000627 NP_038699
Location (UCSC) Chr 6:
160.1 – 160.18 Mb
Chr 17:
13.01 – 13.02 Mb
PubMed search [1] [2]

Superoxide dismutase 2, mitochondrial, also known as SOD2, is an enzyme which in humans is encoded by the SOD2 gene.

Function[edit]

This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial matrix protein that forms a homotetramer and binds one manganese ion per subunit. This protein transforms toxic superoxide, a byproduct of the mitochondrial electron transport chain, into hydrogen peroxide and diatomic oxygen. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[1]

Clinical significance[edit]

Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), sporadic motor neuron disease, and cancer. A common polymorphism associated with greater susceptibility to various patholiges is found in the mitochondrial leader targeting sequence (Val9Ala).[2] Mice lacking Sod2 die shortly after birth, indicating that unchecked levels of superoxide are incompatible with mammalian life.[3] 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.[4] In Drosophila melanogaster, over-expression of Sod2 has been show to increase lifespan by 20%[5]

SOD2 and Exercise-Induced Cardioprotection[edit]

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. [10], 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)

References[edit]

  1. ^ "Entrez Gene: SOD2 superoxide dismutase 2, mitochondrial". 
  2. ^ Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H (August 2007). "Trends in oxidative aging theories". Free Radic. Biol. Med. 43 (4): 477–503. doi:10.1016/j.freeradbiomed.2007.03.034. PMID 17640558. 
  3. ^ Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ (December 1995). "Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase". Nat. Genet. 11 (4): 376–81. doi:10.1038/ng1295-376. PMID 7493016. 
  4. ^ 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 (December 2003). "Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging". Physiol. Genomics 16 (1): 29–37. doi:10.1152/physiolgenomics.00122.2003. PMID 14679299. 
  5. ^ Curtis, C, et al. (2007). "Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes". Genome Biology 8 (12): R262. doi:10.1186/gb-2007-8-12-r262. PMID 18067683. 

Further reading[edit]

  • Zelko IN, Mariani TJ, Folz RJ (2003). "Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression.". Free Radic. Biol. Med. 33 (3): 337–49. doi:10.1016/S0891-5849(02)00905-X. PMID 12126755. 
  • Faraci FM, Didion SP (2005). "Vascular protection: superoxide dismutase isoforms in the vessel wall.". Arterioscler. Thromb. Vasc. Biol. 24 (8): 1367–73. doi:10.1161/01.ATV.0000133604.20182.cf. PMID 15166009.