Disease relevance of Sod3

• Purification and sequence of rat extracellular superoxide dismutase B secreted by C6 glioma [1].
• In summary, efficient overexpression of ECSOD, but not MnSOD in vivo, results in improved endothelial function in a rat model of hypertension and has important implications for the development of endothelial-based vascular gene therapy [2].
• Reactive oxygen species (ROS) have been implicated in the pathogenesis of rheumatoid arthritis (RA), while antioxidant enzymes, such as extracellular superoxide dismutase (EC-SOD) and catalase, block radical-induced events [3].
• Three days after gene transfer of adenovirus expressing human ECSOD (AdECSOD), the response to ACh was not affected in young rats but was improved in old rats [4].

Psychiatry related information on Sod3

• Gene-transfer of EC-SOD reduces superoxide formation and restores age-associated erectile function and may represent a novel therapeutic target for the treatment of erectile dysfunction [5].

High impact information on Sod3

• While EC-SOD from most mammals is tetrameric and has a high affinity for heparin and heparan sulfate, rat EC-SOD has a low affinity for heparin, does not bind to heparan sulfate in vivo, and is apparently dimeric [6].
• To examine the molecular basis of the deviant physical properties of rat EC-SOD, the cDNAs of the rat and mouse EC-SODs were isolated and the deduced amino acid sequences were compared with that of human EC-SOD [6].
• Extracellular superoxide dismutase (EC-SOD) is a secreted Cu and Zn-containing glycoprotein [6].
• Trientine caused the Cu balance to become negative in diabetic subjects through elevated urinary Cu losses and suppressed elevated EC-SOD [7].
• Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that attenuates brain and lung injury from oxidative stress [8].

Chemical compound and disease context of Sod3

• Adenoviruses containing ECSOD (AdECSOD), ECSOD with deletion of its heparin-binding domain (AdECSOD-HBD), or a control virus (AdLacZ) were injected intravenously into rats [9].

Biological context of Sod3

• Although rat EC-SOD has a high sequence homology with the catalytic center and the polybasic heparin-binding site near the COOH terminus of human EC-SOD C, its NH2-terminal sequence and the sequences flanking the heparin-binding site differ substantially [1].
• These results indicate that furin-dependent processing of EC-SOD is important for determining the tissue distribution and half-life of EC-SOD [8].
• This wide variation in EC-SOD content suggests that the susceptibility to pathologies induced by superoxide radicals in the vascular wall interstitium should vary widely among species [10].
• Upregulation of HO-1 expression by intermittent administration of cobalt protoporphyrin, an inducer of HO-1 protein and activity, resulted in a robust increase in EC-SOD but no significant change in Cu-Zn-SOD [11].
• Similarly, augmented iNOS expression, apoptosis and collagen content in the vascular wall were also reduced by EC-SOD treatment [12].

Anatomical context of Sod3

• Neutrophils and macrophages invading the lung showed an intensive staining for the EC-SOD protein concomitantly with a decrease of the enzyme in the plasma [13].
• In control rats, EC-SOD mRNA was synthesized in macrophages and in cells of the arterial vessel walls and the alveolar septa [13].
• Arterial smooth muscle cells were found to secrete large amounts of EC-SOD and likely are the principal source of the enzyme in the vascular wall [10].
• The presented data demonstrated that in lung tissue the EC-SOD enzyme may have a protective function for activated macrophages, neutrophils, and lympoid tissue-associated epithelial cells [13].
• The EC-SOD concentration in the human arterial wall extracellular space is high enough to efficiently suppress the putative pathological effects of the superoxide radical, such as oxidation of LDL and reaction with nitric oxide to form the deleterious peroxynitrite [10].

Associations of Sod3 with chemical compounds

• Exposure to hyperoxia did not affect the distribution of EC-SOD mRNA and protein [13].
• Immunohistochemistry (IHC) and in situ hybridization (ISH) was used to localize extracellular superoxide dismutase (EC-SOD) and its mRNA in rat lung before and after a lipopolysaccharide (LPS)- and hyperoxia-induced inflammation [13].
• The potency to enhance EC-SOD expression is correlated with the ability of the cAMP analogue to induce cAMP-dependent differentiation in C6 [14].
• Example of interference were stimulation of xanthine oxidase activity, color formation without xanthine oxidase, color formation despite excess Cu-Zn SOD addition, and absorbance changes with cyanide inhibition of EC SOD that were above or below blank values [15].
• Analysis of rat plasma fractionated with Sephadex G-150 showed that each assay (three xanthine oxidase based assays plus a modified pyrogallol assay) detected apparent SOD activity almost entirely at the same molecular weight as rat lung EC SOD [15].

Regulatory relationships of Sod3

• EC-SOD treatment clearly reduced the H2O2 induced expression of HB-EGF in rat aortic smooth muscle cells (RASMC) [16].

Other interactions of Sod3

• Vascular EC-SOD and plasma catalase activities were significantly reduced in diabetic compared with nondiabetic rats (P < 0.05) [11].
• Administration of tin mesoporphyrin, an inhibitor of HO-1 activity, decreased EC-SOD protein [11].
• Treatment of the cells with heparin alone decreased HB-EGF expression by 20%, whereas EC-SOD alone and a co-incubation with EC-SOD and heparin suppressed the induction by 60 and 70%, respectively [16].
• The observation that EC-SOD and iNOS are temporally coregulated after cytokine exposure suggests the possibility of a critical mechanism by which cells might protect .NO and avoid the formation of OONO- during inflammation [17].
• METHODS AND RESULTS: We assessed the expression of EC-SOD and GRP78 mRNA in cultured rat VSMCs by Northern blot analysis [18].

Analytical, diagnostic and therapeutic context of Sod3

• Analysis of EC-SOD by immunohistochemistry indicates an even distribution in the vessel wall, including large amounts of the arterial intima [10].
• Lung EC-SOD recovered by immunoprecipitation after 1 week of O(2) showed strong increases in protein nitrotyrosine and variable, nonsignificant differences in protein carbonyl content [19].
• Western blotting and immunofluorescence assays in vitro showed efficient overexpression of MnSOD and ECSOD with respect to localisation to the mitochondria and extracellular surface, respectively [2].
• In the bronchoalveolar lavage fluid (BALF), only macrophages showed a strong positivity for EC-SOD mRNA while the protein was detected in macrophages and neutrophils [13].
• Furthermore, ischaemia and subsequent reperfusion did not cause any alteration in the binding capacity of EC-SOD C to the cardiac vasculature [20].

References