SOD2

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

Function

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

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]

SOD2 and Exercise-Induced Cardioprotection

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

Further reading