Disease relevance of Sod2

• Paraquat is known to promote formation of the superoxide radical anion inside cells and thus the data have been interpreted as indicating that the cloned superoxide dismutase provides protection in E. coli against damage attributable to free radicals [1].
• Copper-zinc superoxide dismutase (SOD1) plays a protective role against the toxicity of superoxide, and studies in Saccharomyces cerevisiae and in Drosophila have suggested an additional role for SOD1 in iron metabolism [2].
• Onchocerca volvulus superoxide dismutase genes: identification of functional promoters for pre-mRNA transcripts which undergo trans-splicing [3].
• Here we explore the potential of RNAi as a therapy for amyotrophic lateral sclerosis (ALS) caused by mutations in the Cu, Zn superoxide dismutase (SOD1) gene [4].
• We have previously shown that genetic disruption of CuZn SOD (SOD1) in Drosophila imparts a recessive phenotype of reduced lifespan, infertility, and hypersensitivity to oxidative stress [5].

High impact information on Sod2

• RNA interference-mediated silencing of Sod2 in Drosophila leads to early adult-onset mortality and elevated endogenous oxidative stress [6].
• In sharp contrast, ablation of SOD2 has no overt effect on the development of larvae and pupae, which may reflect a fundamental transition in oxygen utilization andor reactive oxygen metabolism that occurs during metamorphosis from larval to adult life [6].
• Mutations in Cu/Zn superoxide dismutase (SOD), a hallmark of familial amyotrophic lateral sclerosis (FALS) in humans, are shown here to confer striking neuropathology in Drosophila [7].
• Subunit-destabilizing mutations in Drosophila copper/zinc superoxide dismutase: neuropathology and a model of dimer dysequilibrium [7].
• Furthermore, compound mutants doubly deficient for uric acid and Cu/Zn-containing superoxide dismutase are synthetic lethals, which are unable to complete metamorphosis under normal growth conditions [8].

Biological context of Sod2

• The introduction of additional transgenes encoding Mn-SOD or thioredoxin reductase in the same genetic background also failed to cause life span extension [9].
• Superoxide dismutase activities in long-lived Drosophila melanogaster females: chico (1) genotypes and dietary dilution [10].
• Results from the present study indicate that elevated CuZn SOD activity, not Mn SOD, is the basis for the relatively high level of SOD activity in the chico (1) homozygotes [10].
• In contrast, overexpression of bcl-2, which also rescues these cells form loss of trophic support, was equally effective in saving the cells in the SOD1 downregulation paradigm [11].
• This caused not only efficient cellular uptake even in the presence of serum, but also inhibition of SOD1 activity and promotion of apoptosis at 100-fold lower concentrations of oligonucleotide [11].

Anatomical context of Sod2

• N-Acetylcysteine and chlorophenylthiol cAMP, which rescue PC12 cells and neurons from the withdrawal of nerve growth factor and other forms of trophic support, did not protect PC12 cells from SOD1 downregulation [11].
• Footprinting and electrophoretic mobility shift assay (EMSA) analyses with extracts from HeLa cells showed that Sp1/Sp3 complexes populate the proximal SOD2 promoter, and that Tat leads to an increase in the binding activity of Sp3 [12].
• The aim of this study was to ascertain the status of CuZn superoxide dismutase (CuZn-SOD) expression in the central nervous system of Drosophila melanogaster [13].
• We have studied the effect of the modulation of SOD1 levels on iron metabolism in a cultured human glial cell line and in a mouse motoneuronal cell line [2].
• Whilst hyaline inclusions, which are strongly immunoreactive to SOD1, are linked to degeneration in SOD1 mutant mouse models, the evidence from human tissue is less consistent and convincing [14].

Associations of Sod2 with chemical compounds

• For both MnSOD and Cu/ZnSOD lines, increased life span was not associated with decreased metabolic activity, as measured by O2 consumption [15].
• Superoxide dismutase activity tended to increase with age whereas glutathione peroxidase activity was undetectable [16].
• Effect of age on superoxide dismutase, catalase, glutathione reductase, inorganic peroxides, TBA-reactive material, GSH/GSSG, NADPH/NADP+ and NADH/NAD+ in Drosophila melanogaster [16].
• Death induced by SOD1 downregulation appeared to require the reaction of superoxide with nitric oxide (NO) to form peroxynitrite [11].
• Regulation of the basal manganese superoxide dismutase (SOD2) promoter depends on the transcriptional activity of the Sp family of transcription factors [12].

Other interactions of Sod2

• The overexpression of antioxidative enzymes such as CuZn-superoxide dismutase (SOD), Mn-SOD, and catalase has previously been reported to extend life span in transgenic flies (Drosophila melanogaster) [9].
• However, overall SOD activity, and CuZn SOD or Mn SOD activities did not differ among the diets tested [10].
• Molecular analysis has revealed that the Df(2R)Sod2-332 deletion completely uncovered both MnSOD and its adjacent gene, Arp53D, whereas Df(2R)Sod2-11 was missing the promoter region of MnSOD gene [17].

Analytical, diagnostic and therapeutic context of Sod2

• Microinjection and mobilization of a transgene, which contained a 9-kb genomic sequence encoding Mn SOD, produced 15 experimental lines overexpressing Mn SOD by 5-116% relative to the parental y w strain [18].
• Sequence analysis of the promoter domain is presented, revealing multiple sequence similarities between catalase and Cu,Zn superoxide dismutase promoter domains [19].
• In this study, cDNA encoding the manganese-containing SOD (MnSOD) from the silkworm, Bombyx mori, was isolated by reverse transcriptase-polymerase chain reaction and sequenced [20].
• In recent years, attempts have been made to increase longevity in animal models (caloric restriction in rodents or overexpression of catalase and superoxide dismutase in transgenic flies, for instance) [21].
• The dissection of the regulatory controls that drive the expression of SOD1 may provide further insight into the functional significance of this enzyme [22].

References