Disease relevance of Sod1

• Using mice bearing a disruption of the CuZn-SOD gene (Sod1), the present study was designed to clarify the role of superoxide anion in the pathogenesis of selective vulnerability after transient global ischemia [1].
• These results together suggest that a lesser degree of oxidative damage and a more inducible CuZnSOD activity observed in the mesolimbic dopaminergic pathway may partially explain the differential toxicity MPTP produced in these two dopaminergic systems [2].
• Glioma cells that stably overexpressed CuZnSOD demonstrated additional suppressive effects on the malignant phenotype when compared with the parental cells and vector controls [3].
• We evaluated this possibility in the model of transient focal cerebral ischemia in mice bearing a disruption of the CuZn-SOD gene (Sod1) [4].
• The Sod1 +/- animals also had increased infarct volume and brain swelling, accompanied by increased apoptotic neuronal cell death as indicated by the in situ nick-end labeling technique to detect DNA fragmentation and morphological criteria [4].

Psychiatry related information on Sod1

• The activity of CuZnSOD is increased in patients who suffer from Down's Syndrome, Alzheimer's disease, and in Parkinson's disease [5].

High impact information on Sod1

• Copper-zinc superoxide dismutase (CuZnSOD, SOD1 protein) is an abundant copper- and zinc-containing protein that is present in the cytosol, nucleus, peroxisomes, and mitochondrial intermembrane space of human cells [6].
• To investigate the possible involvement of Cu/Zn-superoxide dismutase (CuZnSOD) gene dosage in the neuropathological symptoms of Down's syndrome, we analyzed the tongue muscle of transgenic mice that express elevated levels of human CuZnSOD [7].
• The findings suggest that CuZnSOD gene dosage is involved in the pathological abnormalities of tongue NMJ observed in Down's syndrome patients [7].
• The results show that expression of elevated levels of CuZnSOD decreases pulmonary oxygen toxicity and associated histologic damage and mortality [8].
• Upon exposure to hyperoxia (greater than 99% O2, 630 torr) the transgenic CuZnSOD mice showed increased survival, decreased morphologic evidence of lung damage such as edema and hyaline membrane formation, and reduction in the number of lung neutrophils [8].

Chemical compound and disease context of Sod1

• The reduction in CuZnSOD was restored by transfection with a GMF/adenovirus construct, and the resulting increase was blocked by the p38 MAP kinase inhibitor SB203580 [9].
• Patients with Down's syndrome (DS) exhibit elevated activity of copper zinc superoxide dismutase (CuZnSOD) caused by the trisomy 21 state [10].
• These findings suggest that CuZnSOD gene dosage is affecting the dense granule transport system and is thereby involved in the depressed level of blood serotonin found in patients born with Down's syndrome [11].
• Gene dosage of CuZnSOD and Down's syndrome: diminished prostaglandin synthesis in human trisomy 21, transfected cells and transgenic mice [10].
• An adenovirus encoding CuZnSOD protects cultured striatal neurones against glutamate toxicity [12].

Biological context of Sod1

• Increasing oxidative stress by combining deficiencies in Atm and superoxide dismutase 1 (Sod1) exacerbated growth retardation and markedly reduced the mean survival time following ionizing radiation [13].
• We observed significant increases in lipid peroxidation and triglyceride (TG) in the liver of Sod1 KO and double KO mice but not in the liver of Sod2 KO mice [14].
• Whereas the phenotype of the Sod1 mutant animals did not differ from that of their normal littermates, the growth of Sod1-/- fetal fibroblasts was only 25% of that of the -/+ and +/+ cells [15].
• This work suggested that CuZnSOD is a new tumor suppressor gene [3].
• MnSOD was decreased during S-phase compared with G0, whereas CuZnSOD was increased during S-phase compared with G0, demonstrating alteration of SOD activities with varying phases of the cell cycle [16].

Anatomical context of Sod1

• When cultured cells were subjected to treatment with paraquat to assess their ability to grow in the presence of high levels of superoxide radicals, Sod1-/- cells were 80 times more sensitive and Sod2-/- cells were 12 times more sensitive to paraquat than wild-type cells [15].
• The investigations of Sod1 transgenic cell-lines and mice, as well as Gpx1 knockout mice (both models favor H(2)O(2) accumulation), are presented [17].
• All of the anti-oxidant enzyme activities were lower in general in the 2 transformed cell lines than in the in vitro normal cell line, except Cu-ZnSOD, which showed little change [18].
• Our results suggest that CuZnSOD-deficient cells are more sensitive to oxygen toxicity than are MnSOD-deficient cells, that paraquat causes free radical-induced damage in both the mitochondria and cytoplasm, and that SOD compartmentalized in the cytosol cannot compensate for the loss of SOD in the mitochondria and vice versa [15].
• In human, all the enzymes (except for catalase) were expressed in MII oocytes and Cu-Zn-SOD was particularly highly expressed [19].

Associations of Sod1 with chemical compounds

• However, it has been suggested that H2O2 production, via Sod1 dismutation, is rate-limited by the availability of the substrate O2*-, and therefore age-related changes may occur as a result of other functions of Sod1 [20].
• Because Sod1 (Cu/ZnSOD) and alphaB crystalline were expressed only in spleen, and protein tyrosine kinase and platelet membrane glycoprotein lib were expressed in both spleen and lung, these genes may also be potential markers for detection of radiation exposure, especially low-dose radiation, in these tissues [21].
• Inhibition by hypericin in the dark was demonstrated for purified CuZnSOD, Se-dependent glutathione peroxidase, glutathione S-transferase, and glutathione reductase activities in vitro [22].
• Copper zinc superoxide dismutase (CuZnSOD) is an essential primary antioxidant enzyme that converts superoxide radical to hydrogen peroxide and molecular oxygen in the cytoplasm [3].
• Furthermore, the protective effect of CuZnSOD at the DNA level, as shown by reduced thymine glycol generation, was demonstrated in paraquat-treated transgenic fibroblasts [23].

Regulatory relationships of Sod1

• The increased CuZnSOD activity in the brain (1.9-fold) of transgenic mice resulted in an enhanced rate of basal lipid peroxidation and in increased MnSOD activity in the 3 age groups [24].

Other interactions of Sod1

• We also found that high fat diet enhanced fatty changes of the liver in Sod1 KO and double KO mice but not in Sod2 KO mice [14].
• CuZnSOD and catalase activities peaked within 0.5 h following irradiation for nontoxic 0.5 microM hypericin and toxic 1.0 microM hypericin [22].
• Previously, we demonstrated that a perturbation in the Sod1-to-Gpx1 ratio, as a consequence of Sod1 overexpression, leads to senescence-like changes [20].
• Five of these represented genes that mapped within the Sod-1 to Ets-2 interval, which was shown previously to contain the weaver (wv) gene [25].
• The other markers included in this study were Prm-1, Gap43 and Sod-1 [26].

Analytical, diagnostic and therapeutic context of Sod1

• METHODS: 10 Cu/ZnSOD gene (Cu/Zn superoxide dismutase gene, Sod1) knockout mice and 16 wild-type mice were analyzed by nested polymerase chain reaction (PCR) [27].
• To investigate this hypothesis, they crossed the Gpx-1 -/- mouse with the Sod-1 tg and subjected the cross to a mouse model of ischemia/reperfusion [28].
• 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 [29].
• In order to test this hypothesis, cell and animal models of CuZnSOD overexpression have been designed [30].
• The amount of CuZnSOD mRNA in each tissue, measured by densitometry of the Northern blot autoradiograms, correlates with the enzymatic activity based on protein content [31].

References