• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3955-3961
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• 2013

Background: Defects of manganese superoxide dismutase (MnSOD) have long been implicated in generation of oxidative stress and risk susceptibility to various cancers. Two functional polymorphisms within the MnSOD gene, including the Val-9Ala of the mitochondrial targeting sequence (MTS) and the Ile58Thr of the exon-3, have been proposed to reduce its enzyme activity and antioxidant potential. Materials and Methods: A high-throughput multiplex SNaPshot$^{(R)}$ system was developed herein for simultaneous analyses of Val-9Ala and Ile58Thr in a single reaction. Genomic DNA extracted from each whole blood sample of 248 patients including 107 with cervical cancer and 141 with breast cancer and from 136 healthy women as controls was analyzed by the multiplex SNaPshot$^{(R)}$ system. Results: The Val/Val, Val/Ala genotypes and the Val allele of the MTS were predominant in patients with cervical or breast cancer as well as healthy women in Thailand. The Ile/Ile genotype and the Ile allele of the exon-3 were found in all of them whereas none of the Ile/Thr, the Thr/Thr genotypes and the Thr allele was detected. Genotypic association of both Val-9Ala and Ile58Thr polymorphisms with cervical cancer and breast cancer of these patients comparing to healthy women was not statistically significant (p<0.05). Conclusions: The Val/Val, Val/Ala genotypes and the Val allele of the MTS were found predominantly but the Ile/Ile genotype and the Ile allele of the exon-3 were detected in patients with cervical cancer, breast cancer and healthy women in Thailand. These two functional polymorphisms (Val-9Ala and Ile58Thr) in MnSOD gene did not associate with susceptibility risk of these cancer patients in Thailand.

• Journal of Microbiology and Biotechnology
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• v.8 no.4
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• pp.305-309
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• 1998

The superoxide dismutase (SOD) activity of seven Bifidobacterium spp. strains was examined by an indirect SOD assay method. Some Bifidobacterium spp. showed significant levels of SOD activity. However, we could not observe any significant differences between anaerobic and aerobic cultures. Furthermore, although several Bifidobacterium spp. exhibited some degree of tolerance to paraquat which produces superoxide radicals, the apparent SOD activity of these strains was not correlated with their resistance to paraquat. In addition, when we added increasing amounts of manganese or iron to MRS medium which had been prepared without either of the metal ions, the apparent SOD activity of cell free extracts (CFEs) was increased with increasing concentration of both metal ions. To our surprise, the heat-denatured CFEs also showed nearly identical correlative patterns. Based on these results, the apparent SOD activity was likely due to a nonenzymatic dismutation. These results strongly suggest that high concentration of divalent metal ions ($Mn^{2+}$, $Fe^{2+}$) in MRS medium result in nonenzymatic dismutation which can lead to false positive SOD activities in Bifidobacerium spp.

• BMB Reports
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• v.32 no.6
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• pp.585-593
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• 1999

The water and methanol extracts of Artemisia argyi showed significant cytotoxicities against J774A.1 cells but not so much against normal leukocytes. The cytotoxicities were found to be dependent on the extract concentration and the incubation time. The concentration of water and methanol extracts inhibiting 50% of cell proliferation ($IC_{50}$) were estimated to be 44.2 mg/ml and 71.6 mg/ml, respectively. In the presence of Artemisia argyi water extract, total superoxide dismutase (CuZnSOD and MnSOD) activities of media, cytoplasmic and mitochondrial fractions of J774A.1 cells increased in accordance with cytotoxicity. MnSOD was found to be the main component of enhanced total SOD activities, particulary in the mitochondrial fraction. In contrast to SOD, catalase and glutathione peroxidase (GPx) were not found in any instance of the current investigation. In addition, substantial amount of $O_2^-$ appeared to be generated in the mitochondrial fraction under the influence of Artemisia argyi. All data put together, it is postulated that Artemisia argyi extracts seem to stimulate $O_2^-$ generation in mitochondria of J774A.1 cells with concomitant increases of SODs. Since $H_2O_2$, the reaction product of SOD on $O_2^-$, is known to be readily converted to very toxic $OH{\cdot}$ in the absence of catalase and/or GPx cooperation, toxicity derived from ROS such as $O_2^-$, $H_2O_2$, and $OH{\cdot}$ may be the main cause of necrosis and/or apoptosis of J774A.1 cells.

• Natural Product Sciences
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• v.19 no.1
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• pp.49-53
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• 2013

Paeonia lactiflora Pall (PL) has been used as a traditional herbal medicine in China, Korea, and Japan for more 1,200 years. PL has reported to have antioxidant activity and protective effect of cells from oxidative stress, although the mechanism has not been verified. FOXO3a is a transcription factor that binds to its target gene's consensus FOXO binding site. FOXO3a protein modulates the various biological functions including cell cycle control, apoptosis, DNA repair, and ROS detoxification. Therefore, FOXO3a activity is associated with cancer, aging, diabetes, infertility, neurodegeneration, and immune system dysfunction. Here we found that FOXO3a was activated by PL extract. Transcriptional target genes such as MnSOD, p27, and GADD45 were activated by PL extract. Protein levels of MnSOD and catalase were increased, consequently, ROS level was reduced in HEF cells by PL extract. These findings suggest that PL extract has an antioxidant activity through FOXO activation and thereby activation of FOXO target genes, MnSOD and catalase.

• Journal of Microbiology and Biotechnology
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• v.10 no.5
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• pp.700-706
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• 2000

Iron- and zinc-containing superoxide dismutase (FeZnSOD) and nickel-containing superoxide dismutase (NiSOD) are cytoplamic enzymes in Streptomyces griseus. The sodF gene coding for FeZnSOD was cloned from genomic Southern hybridization analysis with a 0.5-kb DNA probe, which was PCR-amplified with facing primers corresponding to the N-terminal amino acid of the purified FeZnSOD of S. griseus and a C-terminal region which is conserved among bacterial FeSODs and MnSODs. The sodF open reading frame (ORF) was comprised of 213 amino acid (22,430 Da), and the deduced sequence of the protein was highly homologous (86% identity) to that of FeZnSOD of Streptomyces coelicolor. The FeZnSOD expression of exponentially growing S. griseus cell was approximately doubled as the cell growth reached the early stationary phase. The growth-associated expression of FeZnSOD was mainly controlled at the transcriptional level, and the regulation was exerted through the 110 bp regulatory DNA upstream from the ATG initiation codon of the sodF gene.

• Toxicological Research
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• v.31 no.1
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• pp.17-23
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• 2015

Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors, including memory deficits, decreased motor skills and psychotic behavior resembling Parkinson's disease. Hereditary hemochromatosis (HH) is a prevalent genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major cause of HH. Our previous study has demonstrated that olfactory Mn uptake is altered by HFE deficiency, suggesting that loss of HFE function could alter manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout ($Hfe^{-/-}$) and wild-type ($Hfe^{+/+}$) mice were intranasally-instilled with manganese chloride ($MnCl_2$ 5 mg/kg) or water daily for 3 weeks and examined for memory function. Olfactory Mn diminished both short-term recognition and spatial memory in $Hfe^{+/+}$ mice, as examined by novel object recognition task and Barnes maze test, respectively. Interestingly, $Hfe^{-/-}$ mice did not show impaired recognition memory caused by Mn exposure, suggesting a potential protective effect of Hfe deficiency against Mn-induced memory deficits. Since many of the neurotoxic effects of manganese are thought to result from increased oxidative stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in $Hfe^{+/+}$ mice, but not in $Hfe^{-/-}$ mice. In addition, Hfe deficiency up-regulated SOD1 and glutathione peroxidase activities. These results suggest a beneficial role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC. Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the PFC, indicating that blunted acetylcholine signaling could contribute to impaired memory associated with intranasal manganese. Together, our model suggests that disrupted cholinergic system in the brain is involved in airborne Mn-induced memory deficits and loss of HFE function could in part prevent memory loss via a potential up-regulation of anti-oxidant enzymes in the PFC.

• Proceedings of the Korea Society of Poultry Science Conference
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• 2004.11a
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• pp.33-34
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• 2004

Effect of dietary 2.0 % brown seaweed(Undaria pinnatifida) with bean extract on anti-oxidant system and TNF-$\alpha$ levels were evaluated in blood of 2 week-old broiler chicks activated innate immune response. Dietary brown seaweed and activation of innate immune response decreased MnSOD activities. while activation of innate immune reponse only increased CuZnSOD activities in erythrocyte cytosol. Activation of innate immune response lowered plasma SOD activity in birds fed seaweed with bean extract, increased peroxide levels, and decreased peroxidase activity in plasma. Brown seaweed with bean extract reduced TNF-$\alpha$ levels and increased ovotransferrins concentrations in plasma. The result indicated that dietary 2.0 % brown seaweed with bean extract affect innate immune response changing anti-oxidant system and TNF-$\alpha$ levels in broiler chicks.

• Korean Journal of Plant Resources
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• v.10 no.2
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• pp.188-193
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• 1997

Panax ginseng C.A.Meyer,1 to 5 years old were electrophored and were stained for SOD activity. The result indicated a total of 13 distinct form of the enzyme and the pattern of achromatic bands were not different according to ages. Nine of the enzyme activities were eliminated with cyanide or peroxide treatment and were resistant to treatment of chloroform plus ethanol. It suggested that they may be cupro-zinc containing SOD, whereas four were cyanide or peroxide resistant and were eliminated with cholroform plus ethanol treatment. They may be manganese containing SOD. Ginseng roos. 1 to 5 years old were analyzed for their SOD measurement of SOD activities of all extracts, the significant difference of SOD activities were not shown according to ages. All ginseng extracts had the total SOD activities of all extracts, the significant difference of SOD activities were not shown according to ages. All ginseng extracts had the total SOD activities of about 700-800 unit/g of fresh weight. Therefore, the SOD activities from SOD-mimic compounds were higher than one from SOD. The ratio between the SOD activity from SOD-mimic compounds and one from true SOD was approximately 2:1 to 3:1.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.377-384
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• 2017

Activation of protein kinase C (PKC) is closely linked with endothelial dysfunction. However, the effect of $PKC{\beta}II$ on endothelial dysfunction has not been characterized in cultured endothelial cells. Here, using adenoviral $PKC{\beta}II$ gene transfer and pharmacological inhibitors, the role of $PKC{\beta}II$ on endothelial dysfucntion was investigated in cultured endothelial cells. Phorbol 12-myristate 13-acetate (PMA) increased reactive oxygen species (ROS), p66shc phosphorylation, intracellular adhesion molecule-1, and monocyte adhesion, which were inhibited by $PKC{\beta}i$ (10 nM), a selective inhibitor of $PKC{\beta}II$. PMA increased the phosphorylation of CREB and manganese superoxide dismutase (MnSOD), which were also inhibited by $PKC{\beta}i$. Gene silencing of CREB inhibited PMA-induced MnSOD expression, suggesting that CREB plays a key role in MnSOD expression. Gene silencing of $PKC{\beta}II$ inhibited PMA-induced mitochondrial ROS, MnSOD, and ICAM-1 expression. In contrast, overexpression of $PKC{\beta}II$ using adenoviral $PKC{\beta}II$ increased mitochondrial ROS, MnSOD, ICAM-1, and p66shc phosphorylation in cultured endothelial cells. Finally, $PKC{\beta}II$-induced ICAM-1 expression was inhibited by Mito-TEMPO, a mitochondrial ROS scavenger, suggesting the involvement of mitochondrial ROS in PKC-induced vascular inflammation. Taken together, the results suggest that $PKC{\beta}II$ plays an important role in PMA-induced endothelial dysfunction, and that the inhibition of $PKC{\beta}II$-dependent p66shc signaling acts as a therapeutic target for vascular inflammatory diseases.

• Journal of Preventive Medicine and Public Health
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• v.23 no.4 s.32
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• pp.371-390
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• 1990

Production of free radicals of superoxide anion in tissues by cadmium, activities of superoxide dismutase and catalase to protect tissue damages caused by the free radicals and ATPase that plays an important role in energy metabolism at cellular level were investigated. Experiments in vivo were conducted with liver, kidney and testicle tissue homogenates of rats adding $0.05{\sim}0.50mM$ cadmium chloride, and in vivo experiments administering single dose of 5 mg of cadmium/kg of body weight in 0.1% cadmium chloride solution intraperitoneally 48 hours prior to evisceration. Production of superoxide radicals in liver and testicle increased with addition of cadmium in vitro, but not in kidney. In vivo experiments, however, superoxide radicals slightly increased in liver and kidney but not in testicle. Superoxide dismutase (Cu, Zn-SOD and Mn-SOD), catalase and ATPase (total, $Mg^{++}-\;&\;Na^+,\;K^+-$) activity decreased in the presence of cadimium in dose dependent manner. Reduction of these enzyme activities varied not only with dosage of cadmium but also with type of tissue and between in vitro and in vivo experiment.