Disease relevance of Sod3

• The accessibility of these distal airway epithelial cells to in vivo gene transfer through the tracheal route of administration, suggests the potential for in vivo transfer of MnSOD and EC-SOD genes as a future approach in the prevention of pulmonary O2 toxicity [1].
• When stressed by exposure to > 99% oxygen, the EC-SOD null mutant mice display a considerable reduction in survival time compared to wild-type mice and an earlier onset of severe lung edema [2].
• Inoculation of EC-SOD-secreting fibroblasts suppressed both artificial and spontaneous metastatic lung nodules in mouse metastasis models [3].
• Pedicled cremaster muscle flaps from homozygous EC-SOD knockout (EC-SOD-/-) and wild-type (WT) mice were subjected to 4.5-h ischemia and 90-min reperfusion followed by functional and molecular analyses [4].
• In summary, renal EC-SOD expression is decreased during endotoxemia [5].

High impact information on Sod3

• These findings suggest that while under normal physiological conditions other antioxidant systems may substitute for the loss of EC-SOD; when the animal is stressed these systems are unable to provide adequate protection [2].
• Extracellular superoxide dismutase (EC-SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) is a secreted Cu- and Zn-containing tetrameric glycoprotein, the bulk of which is bound to heparan sulfate proteoglycans in the interstitium of tissues [2].
• Anti-metastatic gene therapy utilizing subcutaneous inoculation of EC-SOD gene transduced autologous fibroblast suppressed lung metastasis of Meth-A cells and 3LL cells in mice [3].
• Therefore, in this study we have developed a gene therapy in a mouse model utilizing extracellular SOD (EC-SOD), which is the most prevalent SOD isoenzyme in extracellular fluids [3].
• Extracellular superoxide dismutase (EC-SOD or SOD3) is an important protective enzyme against the toxicity of superoxide radicals that are produced under both physiological and pathophysiological conditions [6].

Biological context of Sod3

• Immunohistochemical analysis showed that EC SOD was abundantly located in the epidermis as well as in the dermis, but the gene expression of EC SOD mRNA was more abundant in the dermis than in the epidermis [7].
• We propose a model that highlights competition between Ets activators and Kruppel-like repressors within the proximal promoter region that determines the level of EC-SOD expression in a particular cell type [6].
• We hypothesized that during endotoxemic ARF, EC-SOD is decreased in the kidney, resulting in increased O(2)(-) and thus decreased vascular NO bioavailability with resultant renal vasoconstriction and ARF [5].
• Pretreatment with AEOL 10150 did not attenuate neutrophil accumulation but significantly reduced NF-kappaB activation and lipid peroxidation in both wild-type and EC-SOD-deficient mice [8].
• Intravenous administration of EC-SOD adenovirus (2 x 10(9) plaque forming units) into tail vein targeted transgene mainly to liver and induced a 3.5- to sevenfold increase in plasma total SOD activity [9].

Anatomical context of Sod3

• There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P < 0.05) [10].
• In conclusion, our data suggest that EC-SOD plays an important role in the protection from skeletal muscle I/R injury caused by excessive generation of reactive oxygen species [4].
• Histological analysis showed diffuse edema and inflammation around muscle fibers, which was more pronounced in EC-SOD-/- mice [4].
• The increase in hemorrhage-induced neutrophil accumulation in the lungs of EC-SOD-deficient mice suggests that EC-SOD might play a role in mediating neutrophil recruitment to the lung [8].
• Obesity significantly increased EC-SOD level in liver, kidney, testis, gastrocnemius muscle, WAT, brown adipose tissue (BAT), and plasma, but significantly decreased the isoenzyme level in lung [11].

Associations of Sod3 with chemical compounds

• The loss of heparin-binding affinity of EC-SOD type C with high affinity for heparin occurred in kidney of obese mice [11].
• The trained mice underwent a 6-wk swimming program (1 h/day, 5 days/wk) in water at 35-36 degrees C. Immunoreactive extracellular SOD (EC-SOD), copper- and zinc-containing SOD (CuZn-SOD), and manganese-containing SOD (Mn-SOD) contents and their mRNA abundance were determined in serum, heart, lung, liver, kidney, and gastrocnemius muscle [12].

Other interactions of Sod3

• There are three forms of SOD: cytosolic Cu-Zn SOD, mitochondrial Mn SOD, and extracellular SOD (EC SOD) [7].
• These suggest that EC SOD participates in the majority of antioxidant systems in the skin, and it may have different defensive roles from Cu-Zn SOD and Mn SOD against UV-induced injury of the skin [7].
• We have examined the protein content and gene expression of three superoxide dismutase (SOD) isoenzymes in eight tissues from obese ob/ob mice, particularly placing the focus on extracellular-SOD (EC-SOD) in the white adipose tissue (WAT) [11].
• Compared with wild-type mice, EC-SOD-deficient mice had increased lung neutrophil accumulation, a 3.9-fold increase in myeloperoxidase activity, a 1.5-fold increase in nuclear factor (NF)-kappaB activation, and a 1.5-fold increase in lipid peroxidation 1 h after hemorrhage [8].
• In the present study, we have used adenoviral gene transfer to determine effect of extracellular SOD (EC-SOD) on atherogenesis in LDL receptor -/- mice [9].

Analytical, diagnostic and therapeutic context of Sod3

• Therefore, this study investigated the distribution of EC SOD in the skin using immunohistochemistry and examining the patterns of EC SOD gene expression following ultraviolet (UV) irradiation in comparison with those of Cu-Zn SOD and Mn SOD in mouse dorsal skin using Northern blot analysis [7].
• These data indicate the feasibility of anti-metastatic gene therapy utilizing the EC-SOD gene [3].
• Real-time PCR showed that basal expression of EC-SOD was considerably higher in MLg cells compared with the other cell types [6].
• In particular, there was a delayed and incomplete recovery of arterial spasm and blood flow during reperfusion, and more severe acute inflammatory reaction and muscle damage were noted in EC-SOD-/- mice [4].

References