| superoxide dismutase 1 | OKDB#: 171 |
| Symbols: | SOD1 | Species: | human | ||
| Synonyms: | ALS, SOD, ALS1, IPOA, STAHP, hSod1, HEL-S-44, homodimer | Locus: | 21q22.11 in Homo sapiens |
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| General Comment |
Reactive oxygen species in ovarian physiology. Sugino N et al. (2018) Cells living under aerobic conditions always face oxygen paradox. Oxygen is necessary for cells to maintain their lives. However, reactive oxygen species such as superoxide radical ( ), hydroxyl radical (OH-) and hydrogen peroxide (H2O2) are generated from oxygen and damage cells. Oxidative stress occurs as a consequence of excessive production of reactive oxygen species and impaired antioxidant defense systems. Antioxidant enzymes include: superoxide dismutase (SOD), which is a specific enzyme to scavenge superoxide radicals; copper-zinc SOD, located in the cytosol; and manganese SOD, located in the mitochondria. Both types of SOD belong to the first enzymatic step to scavenge superoxide radicals. It has been reported that a number of local factors such as cytokines, growth factors and eicosanoids are involved in the regulation of ovarian function, in addition to gonadotropins and ovarian steroid hormones. Since reactive oxygen species are generated and SOD is expressed in the ovary, there is a possibility that reactive oxygen species and SOD work as local regulators of ovarian function. The present review reports that reactive oxygen species and their scavenging systems play important roles in several processes of reproductive physiology, including follicular development, oocyte maturation, ovulation, corpus luteum function and follicular atresia. (Reprod Med Biol 2005; 4: 31- 45).//////////////////
Superoxide dismutase was discovered by Fridovich et al. (1975). Known for over 30 years as a copper-containing, low molecular weight cytoplasmic protein, erythrocuprein (SOD) was shown in 1969 to catalyze the disproportionation of superoxide radicals to molecular oxygen and hydrogen peroxide. The name came from the fact that the reaction is a dismutation of superoxide anions. The 2 distinct forms of superoxide dismutase have different immunologic specificities. SOD1is a copper- and zinc-containing enzyme. SOD2 is a manganese-containing enzyme. SOD1 is a dimer whereas SOD2 is a tetramer.
NCBI Summary: The protein encoded by this gene binds copper and zinc ions and is one of two isozymes responsible for destroying free superoxide radicals in the body. The encoded isozyme is a soluble cytoplasmic protein, acting as a homodimer to convert naturally-occuring but harmful superoxide radicals to molecular oxygen and hydrogen peroxide. The other isozyme is a mitochondrial protein. Mutations in this gene have been implicated as causes of familial amyotrophic lateral sclerosis. Rare transcript variants have been reported for this gene. [provided by RefSeq, Jul 2008] |
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| General function | Enzyme, Oxidoreductase | ||||
| Comment | SOD is involved in the elimination of reactive oxygen species (ROS). ROS have been implicated in a wide range of degenerative processes including amyotrophic lateral sclerosis, ischemic heart disease, Alzheimer disease, Parkinson disease, and aging. ROS are generated by mitochondria as the toxic by-products of oxidative phosphorylation, their energy generating pathway. | ||||
| Cellular localization | Cytoplasmic, Nuclear | ||||
| Comment | Oxidative stress but not endothelial dysfunction exists in non-obese, young group of patients with polycystic ovary syndrome. Kuşçu NK et al. (2009) To determine if oxidative stress and endothelial dysfunction exist at the same time in a young, non-obese group of patients with polycystic ovary syndrome (PCOS). Cross-sectional study. Celal Bayar University, School of Medicine, Manisa, Turkey. Thirty-one young, non-obese patients with PCOS and 23 age- and body mass index-matched controls. Following clinical and biochemical diagnosis, malonyldialdehyde (MDA), superoxide dismutase (SOD), von Willebrand Factor (vWF), and nitric oxide (NO) levels of patients and controls were measured and compared. To find out oxidative stress and endothelial dysfunction parameters. MDA (0.12+/-0.03 vs 0.10+/-0.03, p=0.01) and SOD (8.0+/-0.7 vs 7.28+/-0.8, p=0.001) levels were significantly higher in PCOS group while there was no difference in vWF (527.2+/-280.1 vs 568.1+/-276.8, p>0.05) and NO levels (169.9+/-47.4 vs 168.9+/-80, p>0.05). When the results of the PCOS patients were divided into two subgroups in terms of insulin resistance (IR- and IR + ), the IR- subgroup had significantly higher MDA levels compared to the control (0.125+/-0.03 vs 0.101+/-0.03, p=0.03). Though IR+ group also had higher MDA than the control group, it did not reach to a significant level (0.117+/-0.05 vs 0.101+/-0.03, p>0.05). Both IR- and IR+ groups had significantly higher SOD levels compared with control group (7.99+/-0.7 vs 7.28+/-0.8, p=0.009 and 8.22+/-0.8 vs 7.28+/-0.8, p=0.03, respectively). vWF and NO levels were not different among these three groups (p>0.05). Oxidative stress is prominent while endothelial dysfunction does not exist in young, non-obese patients with PCOS.////////////////// SOD1 is present in both cytoplasmic and nuclear compartments whereas SOD2 is localized to mitochondria. Impaired Fertilizing Ability of Sod1-Deficient Mouse Sperm During In Vitro Fertilization. Tsunoda S et al. The oxidative modification of gametes by a reactive oxygen species is a major deleterious factor that decreases the successful rate of in vitro fertilization. Superoxide dismutase 1 (SOD1) plays a pivotal role in antioxidation by scavenging the superoxide anion, and its deficiency causes infertility in female mice, but the significance of the enzyme in male mice remains unclear. In the present study, we characterized Sod1(-/-) (Sod1-KO) male reproductive organs and compiled the first report of the impaired fertilizing ability of Sod1-KO sperm in in vitro fertilization. Insemination of wild-type (WT) oocytes with Sod1-KO sperm exhibited lower rates of fertility compared with insemination by wild-type sperm. The low fertilizing ability found for Sod1-KO sperm was partially rescued by reductant 2-mercaptoethanol, which suggested the oxidative modification of sperm components. The numbers of motile and progressive sperm decreased during the in vitro fertilization process, and a decline in ATP content and elevation in lipid peroxidation occurred in the Sod1-KO sperm in an incubation time-dependent manner. Tyrosine phosphorylation, which is a hallmark for sperm capacitation, was also impaired in the Sod1-KO sperm. These results collectively suggest that machinery involved in the sperm capacitation and motility are vulnerable to oxidative damage during the in vitro fertilization process, which could increase the rate of inefficient fertilization. | ||||
| Ovarian function | Steroid metabolism, Luteinization, Luteolysis, Oogenesis, Oocyte maturation | ||||
| Comment | Oxidative stress in oocytes during midprophase induces premature loss of cohesion and chromosome segregation errors. Perkins AT et al. (2016) In humans, errors in meiotic chromosome segregation that produce aneuploid gametes increase dramatically as women age, a phenomenon termed the "maternal age effect." During meiosis, cohesion between sister chromatids keeps recombinant homologs physically attached and premature loss of cohesion can lead to missegregation of homologs during meiosis I. A growing body of evidence suggests that meiotic cohesion deteriorates as oocytes age and contributes to the maternal age effect. One hallmark of aging cells is an increase in oxidative damage caused by reactive oxygen species (ROS). Therefore, increased oxidative damage in older oocytes may be one of the factors that leads to premature loss of cohesion and segregation errors. To test this hypothesis, we used an RNAi strategy to induce oxidative stress in Drosophila oocytes and measured the fidelity of chromosome segregation during meiosis. Knockdown of either the cytoplasmic or mitochondrial ROS scavenger superoxide dismutase (SOD) caused a significant increase in segregation errors, and heterozygosity for an smc1 deletion enhanced this phenotype. FISH analysis indicated that SOD knockdown moderately increased the percentage of oocytes with arm cohesion defects. Consistent with premature loss of arm cohesion and destabilization of chiasmata, the frequency at which recombinant homologs missegregate during meiosis I is significantly greater in SOD knockdown oocytes than in controls. Together these results provide an in vivo demonstration that oxidative stress during meiotic prophase induces chromosome segregation errors and support the model that accelerated loss of cohesion in aging human oocytes is caused, at least in part, by oxidative damage.////////////////// Deregulation of the Sod1 and Nd1 genes in mouse fetal oocytes exposed to mono-(2-ethylhexyl) phthalate (MEHP). Bonilla E et al. Mono-(2-ethylhexyl) phthalate (MEHP) is the active metabolite of the diester (DEHP), a well-known reproductive toxicant. Since, different molecular mechanisms underlying this toxicity are not well understood, the effects of MEHP on cell viability and gene expression were assessed in murine fetal oocytes cultured in vitro. Oocyte survival decreased significantly after a 24h exposure to MEHP and hence, the effects of MEHP on changes in gene expression were analyzed using cDNA libraries and differential screenings. In these assays, the genes that suffered the most severe deregulation corresponded to those encoding Cu-Zn superoxide dismutase (Sod1) and a mitochondrial respiratory chain protein (Nd1). Indeed, functional assays on somatic cells transfected with a Sod1 luciferase reporter construct demonstrated its specific MEHP dose-dependent upregulation, confirming that the expression of this gene is deregulated in response to MEHP. | ||||
| Expression regulated by | LH, prolactin, estradiol, dexamethasone | ||||
| Comment | Sugino et al. (2000) studied the effects of human chorionic gonadotrophin (HCG) on luteal SOD in vitro. HCG significantly increased Cu,Zn-SOD expression in mid-luteal phase corpora lutea, but not in late luteal phase corpora lutea. Gene expression increased. Luteinization of porcine preovulatory follicles leads to systematic changes in follicular gene expression. Agca C et al. The LH surge initiates the luteinization of preovulatory follicles and causes hormonal and structural changes that ultimately lead to ovulation and the formation of corpora lutea. The objective of the study was to examine gene expression in ovarian follicles (n = 11) collected from pigs (Sus scrofa domestica) approaching estrus (estrogenic preovulatory follicle; n = 6 follicles from two sows) and in ovarian follicles collected from pigs on the second day of estrus (preovulatory follicles that were luteinized but had not ovulated; n = 5 follicles from two sows). The follicular status within each follicle was confirmed by follicular fluid analyses of estradiol and progesterone ratios. Microarrays were made from expressed sequence tags that were isolated from cDNA libraries of porcine ovary. Gene expression was measured by hybridization of fluorescently labeled cDNA (preovulatory estrogenic or -luteinized) to the microarray. Microarray analyses detected 107 and 43 genes whose expression was decreased or increased (respectively) during the transition from preovulatory estrogenic to -luteinized (P<0.01). Cells within preovulatory estrogenic follicles had a gene-expression profile of proliferative and metabolically active cells that were responding to oxidative stress. Cells within preovulatory luteinized follicles had a gene-expression profile of nonproliferative and migratory cells with angiogenic properties. Approximately, 40% of the discovered genes had unknown function. | ||||
| Ovarian localization | Oocyte, Cumulus, Granulosa, Theca, Luteal cells, Follicular Fluid | ||||
| Comment | Profiling of SOD isoenzymes in compartments of the developing bovine antral follicle. Combelles C et al. The antral follicle constitutes a complex and regulated ovarian microenvironment that influences oocyte quality. Oxidative stress is a cellular state that may play a role during folliculogenesis and oogenesis, although direct supporting evidence is currently lacking. We thus evaluated the expression of the three isoforms (SOD1, 2, 3) of the enzymatic antioxidant superoxide dismutase in all of the cellular (granulosa cells, cumulus cells, oocytes) and extracellular (follicular fluid) compartments of the follicle. Comparisons were performed in bovine ovaries across progressive stages of antral follicular development. Follicular fluid possessed increased amounts of SOD1, 2, 3 in small when compared to large antral follicles; concomitantly, total SOD activity was highest in follicular fluids from smaller diameter follicles. SOD1, 2, and 3 proteins were expressed in granulosa cells without any fluctuations with follicle sizes. All three SOD isoforms were present but distributed differently in oocytes from small, medium, or large antral follicles. Cumulus cells expressed high levels of SOD3, some SOD2, but no detectable SOD1. Our studies provide a temporal and spatial expression profile of the three SOD isoforms in the different compartments of the developing bovine antral follicles. These results lay the ground for future investigations into the potential regulation and roles of antioxidants during folliculogenesis and oogenesis. Superoxide Dismutase expression in human cumulus oophorus cells. Matos L et al. Success in Assisted Reproductive Techniques (ART) is influenced by gamete and embryo quality but the assessment of these parameters has been thwarted by the lack of reliable biomarkers. Follicular fluid and cumulus oophorus cells may provide biomarkers due to their close relationship to the oocyte. These cells produce antioxidants and thus protect the oocyte from oxidative damage exerted by reactive oxygen species (ROS). ROS and antioxidants are known to intervene in reproductive physiology and pathology, but their roles are unclear. It is hypothesized that Superoxide Dismutase (SOD), a first line antioxidant enzyme, is associated with oocyte quality. Cells obtained in the course of ART for the treatment of infertility due to male factor or female pathology were processed for SOD intracellular isoforms (CuZnSOD and MnSOD) immunodetection, total SOD activity and isoforms content. Cells presented strong positive staining for CuZnSOD and MnSOD. SOD activity decreased with increasing female age but was increased in endometriosis and in ovulatory dysfunction. When male factor was the cause for infertility, successful ART was associated with higher SOD activity. Variations in SOD emphasize the relevance of oxidative stress in the oocyte maturation process. These variations also suggest that SOD is a potential biomarker for ART success. Suzuki et al. (1999) investigated the expression of manganese (Mn) (SOD2) and copper-zinc (Cu,Zn) superoxide dismutase (SOD1) in normal cycling human ovaries throughout the menstrual cycle. They reported that, in the follicular stage, SOD2 immunoreactivity was detected in granulosa and theca interna cells of steroid-producing follicles, that is, preantral, nondominant, dominant, and atretic follicles, whereas SOD2 was detected in theca interna cells of these follicles and in granulosa cells of dominant follicles. In the luteal stage, immunoreactivity for Mn-SOD and Cu,Zn-SOD was observed in both luteinized granulosa and theca cells of the functioning corpus luteum. In the early degenerating corpus luteum, both Mn-SOD and Cu,Zn-SOD were positive in steroid-producing luteinized theca cells. Mn-SOD immunoreactivity was also detected in nonsteroid-producing luteinized granulosa cells and macrophages. The results suggest that the expression of Mn-SOD and Cu,Zn-SOD closely correlates with steroidogenesis in the human ovary. Sabatini et al.(1999) reported that superoxide dismutase (SOD) activity is present in human follicular fluid and is higher than in serum. The degree of SOD activity is variable and seems to be inversely related to the fertilization of oocytes. Sugino et al. (2000) reported that in the pregnant human corpus luteum, Cu,Zn-SOD activities were significantly higher than those in the mid-luteal phase. In contrast, manganese SOD (Mn-SOD) activities were low in the mid-luteal phase and increased toward the regression phase. Changes in mRNA expression of both types of SOD were similar to changes in their activities. | ||||
| Follicle stages | Secondary, Antral, Preovulatory, Corpus luteum | ||||
| Comment | Higher SOD1 Gene Expression in Cumulus Cells From Infertile Women With Moderate and Severe Endometriosis. Donabela FC et al. (2015) It is questioned whether worsening of oocyte quality and oxidative stress (OS) are involved in the pathogenesis of infertility related to endometriosis and in compromised intracytoplasmic sperm injection (ICSI) outcomes. Cumulus cells (CCs) protect oocytes from entering apoptosis induced by OS. Thus, we carried out a case-control study comparing expression of superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), and glutathione peroxidase 4 (GPX4; genes encoding for the main antioxidant enzymes) in CCs from mature oocytes of 26 infertile patients with minimal/mild endometriosis, 14 patients with moderate/severe endometriosis, and 41 controls undergoing controlled ovarian stimulation for ICSI, using real-time polymerase chain reaction. As a secondary objective, we investigated the interaction between the expression of these genes and clinical pregnancy (CP) by a statistical model. Only infertile women with moderate/severe endometriosis showed increased expression of the SOD1 in CCs compared to women with minimal/mild endometriosis and controls, with a positive interaction between increased expression and the occurrence of CP, suggesting that SOD1 might be a potential biomarker of CP following ICSI.////////////////// | ||||
| Phenotypes | |||||
| Mutations |
4 mutations
Species: mouse
Species: human
Species: mouse
Species: mouse
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| Genomic Region | show genomic region | ||||
| Phenotypes and GWAS | show phenotypes and GWAS | ||||
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| created: | Oct. 19, 1999, midnight | by: |
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| last update: | March 18, 2020, 3:40 p.m. | by: | hsueh email: |
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