• Title/Summary/Keyword: Manganese Superoxide Dismutase (MnSOD)

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Molecular Cloning and Expression of Sequence Variants of Manganese Superoxide Dismutase Genes from Wheat

  • Baek, Kwang-Hyun;Skinner, Daniel Z.
    • Korean Journal of Environmental Agriculture
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    • v.29 no.1
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    • pp.77-85
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    • 2010
  • Reactive oxygen species (ROS) are very harmful to living organisms due to the potential oxidation of membrane lipids, DNA, proteins, and carbohydrates. transformed E.coli strain QC 871, superoxide dismutase (SOD) double-mutant, with three sequence variant MnSOD1, MnSOD2, and MnSOD3 manganese superoxide dismutase (MnSOD) gene isolated from wheat. Although all QC 871 transformants grown at $37^{\circ}C$ expressed mRNA of MnSOD variants, only MnSOD2 transformant had functional SOD activity. MnSOD3 expressed active protein when grown at $22^{\circ}C$, however, MnSOD1 did not express functional protein at any growing and induction conditions. The sequence comparison of the wheat MnSOD variants revealed that the only amino acid difference between the sequence MnSOD2 and sequences MnSOD1 and 3 is phenylalanine/serine at position 58 amino acid. We made MnSOD2S58F gene, which was made by altering the phenylalaine to serine at position 58 in MnSOD2. The expressed MnSOD2S58F protein had functional SOD activity, even at higher levels than the original MnSOD2 at all observed temperatures. These data suggest that amino acid variation can result in highly active forms of MnSOD and the MnSOD2S58F gene can be an ideal target used for transforming crops to increase tolerance to environmental stresses.

Isolation and Characterization of the sod2$^{2+}$ Gene Encoding a Putative Mitochondrial Manganese Superoxide Dismutase in Schizosaccharomyces bombe

  • Jeong, Jae-Hoon;Kwon, Eun-Soo;Roe, Jung-Hye
    • Journal of Microbiology
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    • v.39 no.1
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    • pp.37-41
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    • 2001
  • The fission yeast Schizosaccharomyces pombe contains two distinct superoxide dismutase (SOD) activities, one in the cytosol encoded by the $sod2^{+}$ gene and the other in mitochondria. The $sod2^{+}$ gene encoding putative mitochondrial manganese superoxide dismutase (MnSOD) was isolated from the S. pombe genomic library using a PCR fragment as the probe. The nucleotide sequence of the $sod2^{+}$ gene and its flanking region (4051 bp HindIII fragment) was determined. An intron of 123 nt in size was predicted and confirmed by sequencing the cDNA following reverse transcription PCR. The predicted Sod2p consists of 218 amino acid residues with a molecular mass of 24,346 Da. The deduced amino acid sequence showed a high degree of homology with other MnSODs, especially in the metal binding residues at the active site and their relative positions. The transcriptional start site was mapped by primer extension at 231 at upstream from the ATG codon. A putative TATA box(TATAAAA) was located 58 nt upstream from the transcriptional start site and putative polyadenylation sites were located at 1000, 1062, and 1074 nt downstream from the ATG start codon.

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Characterization of Superoxide Dismutase in Lactococcus lactis

  • Chang, Woo-Suk;So, Jae-Seong
    • Journal of Microbiology and Biotechnology
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    • v.9 no.6
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    • pp.732-736
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    • 1999
  • The superoxide dismutase (SOD) in Lactococcus lactis was measured quantitatively and qualitatively under various culture conditions. The L. lactis SOD was induced by oxidative stress. As the concentration of paraquat to produce superoxide radicals increased, the growth of L. lactis decreased with concomitant increase of SOD activity. The SOD activity was found to be growth-phase dependent: when aerobically grown cells entered to the stationary phase, the activity increased gradually until the late stationary phase. From inhibition studies, L. lactis SOD was found to be insensitive to KCN and $H_2O_2$ which are known to inhibit Cu/ZnSOD and FeSOD, respectively. Moreover, as the concentration of manganese in the medium increased, the activity of SOD also increased. These data strongly suggested that L. lactis possessed a single manganese-containing SOD (MnSOD). Finally, a putative sod gene fragment of 510 bp was identified in L. lactis using a polymerase chain reaction (PCR) with degenerate primers designed from the deduced DNA sequences of known SOD genes.

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Bidirectional Regulation of Manganese Superoxide Dismutase (MnSOD) on the Radiosensitivity of Esophageal Cancer Cells

  • Sun, Guo-Gui;Hu, Wan-Ning;Wang, Ya-Di;Yang, Cong-Rong;Lu, Yi-Fang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3015-3023
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    • 2012
  • The mitochondrial antioxidant protein manganese superoxide dismutase (MnSOD) may represent a new type of tumor suppressor protein. Overexpression of the cDNA of this gene by plasmid or recombinant lentiviral transfection in various types of cancer leads to growth suppression both in vitro and in vivo. We previously determined that changes in MnSOD expression had bidirectional effects on adriamycin (ADR) when combined with nitric oxide (NO). Radiation induces free radicals in a manner similar to ADR, so we speculated that MnSOD combined with NO would also have a bidirectional effect on cellular radiosensitivity. To examine this hypothesis, TE-1 human esophageal squamous carcinoma cells were stably transfected using lipofectamine with a pLenti6-DEST plasmid containing human MnSOD cDNA at moderate to high overexpression levels or with no MnSOD insert. Blastidicin-resistant colonies were isolated, grown, and maintained in culture. We found that moderate overexpression of MnSOD decreased growth rates, plating efficiency, and increased apoptosis. However, high overexpression increased growth rates, plating efficiency, and decreased apoptosis. When combined with NO, moderate overexpression of MnSOD increased the radiosensitivity of esophageal cancer cells, whereas high MnSOD overexpression had the opposite effect. This finding suggests a potential new method to kill certain radioresistant tumors and to provide radioresistance to normal cells.

Different Association of Manganese Superoxide Dismutase Gene Polymorphisms with Risk of Prostate, Esophageal, and Lung Cancers: Evidence from a Meta-analysis of 20,025 Subjects

  • Sun, Guo-Gui;Wang, Ya-Di;Lu, Yi-Fang;Hu, Wan-Ning
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.1937-1943
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    • 2013
  • Altered expression or function of manganese superoxide dismutase (MnSOD) has been shown to be associated with cancer risk but assessment of gene polymorphisms has resulted in inconclusive data. Here a search of published data was made and 22 studies were recruited, covering 20,025 case and control subjects, for meta-analyses of the association of MnSOD polymorphisms with the risk of prostate, esophageal, and lung cancers. The data on 12 studies of prostate cancer (including 4,182 cases and 6,885 controls) showed a statistically significant association with the risk of development in co-dominant models and dominant models, but not in the recessive model. Subgroup analysis showed there was no statistically significant association of MnSOD polymorphisms with aggressive or nonaggressive prostate cancer in different genetic models. In addition, the data on four studies of esophageal cancer containing 620 cases and 909 controls showed a statistically significant association between MnSOD polymorphisms and risk in all comparison models. In contrast, the data on six studies of lung cancer with 3,375 cases and 4,050 controls showed that MnSOD polymorphisms were significantly associated with the decreased risk of lung cancer in the homozygote and dominant models, but not the heterozygote model. A subgroup analysis of the combination of MnSOD polymorphisms with tobacco smokers did not show any significant association with lung cancer risk, histological type, or clinical stage of lung cancer. The data from the current study indicated that the Ala allele MnSOD polymorphism is associated with increased risk of prostate and esophageal cancers, but with decreased risk of lung cancer. The underlying molecular mechanisms warrant further investigation.

Manganese Superoxide Dismutase (MnSOD Val-9Ala) Gene Polymorphism and Susceptibility to Gastric Cancer

  • Moradi, Mohammad-Taher;Yari, Kheirollah;Rahimi, Zohreh;Kazemi, Elham;Shahbazi, Mehrdad
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.485-488
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    • 2015
  • Background: Oxidative stress caused by the generation of reactive oxygen species plays an important role in human carcinogenesis. Manganese superoxide dismutase (MnSOD) Val-9Ala in the mitochondrial target sequence is the best known polymorphism of this enzyme. The purpose of the current research was to assess the association of MnSOD Val-9Ala genotypes with the risk of gastric cancer. Materials and Methods: This case-control study covered 54 gastric cancer patients compared to 100 cancer free subjects as controls. Extraction of DNA was performed on bioptic samples and genotypes were identified with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequencies of MnSOD Ala/Ala, Ala/Val and Val/Val genotypes in healthy individuals were 24.3, 66.7 and 9%, respectively. However, in gastric cancer patients, Ala/Ala, Ala/Val and Val/Val were observed in 24.0, 48.0 and 28.0% (p=0.01). In patients the frequency of MnSOD Val allele was higher (52%) compared to that in controls (42%). Conclusions: The results of this study show a positive association between MnSOD Val-9Ala gene polymorphism and risk of gastric cancer disease in Iranian population.

miR-23a Regulates Cardiomyocyte Apoptosis by Targeting Manganese Superoxide Dismutase

  • Long, Bo;Gan, Tian-Yi;Zhang, Rong-Cheng;Zhang, Yu-Hui
    • Molecules and Cells
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    • v.40 no.8
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    • pp.542-549
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    • 2017
  • Cardiomyocyte apoptosis is initiated by various cellular insults and accumulated cardiomyocyte apoptosis leads to the pathogenesis of heart failure. Excessive reactive oxygen species (ROS) provoke apoptotic cascades. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme that converts cellular ROS into harmless products. In this study, we demonstrate that MnSOD is down-regulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Enhanced expression of MnSOD attenuates cardiomyocyte apoptosis and myocardial infarction induced by I/R injury. Further, we show that miR-23a directly regulates the expression of MnSOD. miR-23a regulates cardiomyocyte apoptosis by suppressing the expression of MnSOD. Our study reveals a novel model regulating cardiomyocyte apoptosis which is composed of miR-23a and MnSOD. Our study provides a new method to tackling apoptosis related cardiac diseases.

Changes of superoxide dismutase and glutathione peroxidase in light damaged rat retina

  • Kaidzu, Sachiko;Tanito, Masaki;Takanashi, Taiji;Ohira, Akihiro
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.430-432
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    • 2002
  • The changes in expression of copper-zinc superoxide dismutase (CuZn-SOD), manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase (GPX) in light-damaged rat retinas were examined. Sprague-Dawley rats (male, 6-weeks-old) were maintained on a cyclic photoperiod (12 hours light and 12 hours darkness) for 2 weeks. The illumination intensity during the light period was 80 lux. To induce light damage to the retina, a high-intensity illumination (3000-lux) was applied to the animals for 24 hours. After light exposure, the animals were returned to cyclic lighting. Eyes were enucleated 12 and 24 hours after light exposure started or 1,3, and 7 days after light exposure ended. Eyes were fixed and embedded in paraffin wax. Tissues were cut into 4${\mu}{\textrm}{m}$-thick sections. Sections were immunostained using antibody against CuZn-SOD, Mn-SOD, GPX and 8-hydroxy-deoxyguanocine (8-OHdG) as oxidative stress marker. 8-OHdG was observed in the outer nuclear layer (ONL) and retinal pigment epithelium (RPE) during light exposure. In light-damaged retinas CuZn-SOD labeling was up regulated in the ONL and RPE. Mn-SOD labeling was up regulated in rod inner segments (RIS) during light exposure and that in the RPE was up regulated after exposure. GPX labeling was observed in rod outer segments (ROS) during light exposure. GPX labeling was also observed in the RPE during and after light exposure. All three enzymes were observed in the outer retina, which suffered light damage, but occurred in defferent layers except within the RPE, in which case all three were expressed. These enzymes may play complementary roles as protective factors in light-damaged retinas.

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Effects of Manganese Chloride on Chlorophyll, Free Proline and SOD Activity of Rice Seedling (염화망간 처리가 벼 유묘의 엽록소, 유리 Proline 및 SOD 활성에 미치는 영향)

  • 김상국;이상철
    • Korean Journal of Plant Resources
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    • v.12 no.2
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    • pp.166-169
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    • 1999
  • The experiment was conducted to find the changes of early growth and chemical components such as chlorophyll content, superoxide dismutase(SOD) activity, free proline content on the different manganese chloride concentration(2,500, 3,500 and 4,500ppm) in rice seedling. Root growth was decreased in highest concentration, 4,500 ppm of Mn compared with the control and germination rate was also decreased 43% at 4,500 ppm of Mn. Chlorophyll content was decreased at Mn 4,500ppm with 1.16mg. Free proline content at 3 day after germination in Mn 4,500ppm was highest relative to the other manganese chloride concentrations. SOD activity was gradually increased as manganese chloride concentration was increased. As a result, it was suggested that an increment of free proline and SOD activity results from the higher manganese chloride concentration.

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Modulation of MnSOD in Cancer: Epidemiological and Experimental Evidences

  • Kim, Ae-Kyong
    • Toxicological Research
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    • v.26 no.2
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    • pp.83-93
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    • 2010
  • Since it was first observed in late 1970s that human cancers often had decreased manganese superoxide dismutase (MnSOD) protein expression and activity, extensive studies have been conducted to verify the association between MnSOD and cancer. Significance of MnSOD as a primary mitochondrial antioxidant enzyme is unquestionable; results from in vitro, in vivo and epidemiological studies are in harmony. On the contrary, studies regarding roles of MnSOD in cancer often report conflicting results. Although putative mechanisms have been proposed to explain how MnSOD regulates cellular proliferation, these mechanisms are not capitulated in epidemiological studies. This review discusses most recent epidemiological and experimental studies that examined the association between MnSOD and cancer, and describes emerging hypotheses of MnSOD as a mitochondrial redox regulatory enzyme and of how altered mitochondrial redox may affect physiology of normal as well as cancer cells.