• Toxicological Research
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• v.34 no.4
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• pp.363-370
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• 2018

Many studies reported reduced antioxidant capacity in the vasculature under hypertensive conditions. However, little is known about the effects of antihypertensive treatments on the regulation of vascular antioxidant enzymes. Thus, we hypothesized that antihypertensive treatments prevent the reduction of antioxidant enzyme activity and expression in the small vessels of angiotensin II-induced hypertensive rats (ANG). We observed the small mesenteric arteries and small renal vessels of normotensive rats (NORM), ANG, and ANG treated with a triple antihypertensive therapy of reserpine, hydrochlorothiazide, and hydralazine (ANG + TTx). Systolic blood pressure was increased in ANG, which was attenuated by 2 weeks of triple therapy (127, 191, and 143 mmHg for NORM, ANG, and ANG + TTx, respectively; p < 0.05). Total superoxide dismutase (SOD) activity in the small mesenteric arteries of ANG was lower than that of NORM. The protein expression of SOD1 was lower in ANG than in NORM, whereas SOD2 and SOD3 expression was not different between the groups. Reduced SOD activity and SOD1 expression in ANG was not restored in ANG + TTx. Both SOD activity and SOD isoform expression in the small renal vessels of ANG were not different from those of NORM. Interestingly, SOD activity in the small renal vessels was reduced by TTx. Between groups, there was no difference in catalase activity or expression in both the small mesenteric arteries and small renal vessels. In conclusion, SOD activity in the small mesenteric arteries decreased by angiotensin II administration, but not by hypertension, which is caused by decreased SOD1 expression.

• BMB Reports
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• v.45 no.11
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• pp.659-664
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• 2012

Extracellular superoxide dismutase (EC-SOD) overexpression modulates cellular responses such as tumor cell suppression and is induced by $IFN{\gamma}$. Therefore, we examined the role of EC-SOD in $IFN{\gamma}$-mediated tumor cell suppression. We observed that the dominant-negative protein kinase C delta ($PKC{\delta}$) suppresses $IFN{\gamma}$-induced EC-SOD expression in both keratinocytes and melanoma cells. Our results also showed that $PKC{\delta}$-induced EC-SOD expression was reduced by pretreatment with a PKC-specific inhibitor or a siRNA against $PKC{\delta}$. $PKC{\delta}$-induced EC-SOD expression suppressed cell proliferations by the up-regulation of p21 and Rb, and the downregulation of cyclin A and D. Finally, we demonstrated that increased expression of EC-SOD drastically suppressed lung melanoma proliferation in an EC-SOD transgenic mouse via p21 expression. In summary, our findings suggest that $IFN{\gamma}$-induced EC-SOD expression occurs via activation of $PKC{\delta}$. Therefore, the upregulation of EC-SOD may be effective for prevention of various cancers, including melanoma, via cell cycle arrest.

• Journal of Korean Society of Forest Science
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• v.101 no.1
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• pp.69-76
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• 2012

We investigated the effect of mountain ginseng-added high fat diet supplementation on lipid peroxidation and antioxidant protein expressions in rats. Thirty-two male rats were randomly divided into 4 groups; HS (high-fat diet sedentary group, n=8), MG1 (0.5% mountain ginseng-added diet group, n=8), MG2 (1% mountain ginsengadded diet group, n=8) and MG3 (2% mountain ginseng-added diet group, n=8). They have fed the diet for 4 weeks. The blood triglyceride were significantly lower in the MG1 and MG2 groups than that of the HS group. The blood HDL-cholesterol were significantly higher in the MG3 group than that of the HS and MG2 groups. The muscle glycogen contents of the MG2 and MG3 groups were significantly higher than that of HS and MG1 groups. The MDA contents in the MG1, MG2 and MG3 groups tended to lower than the HS group. The GPx protein expression in the gastrocnemius muscle of the MG2 group was significantly increased compared to that of the HS group. The Cu,Zn-SOD protein expression in the gastrocnemius muscle of the MG1 and MG2 groups was significantly increased compared to that of the MG3 group. The Mn-SOD protein expression in the MG1, MG2 and MG3 groups tended to higher than the HS group. From these results, it was suggested that mountain ginseng-added diet may have an crucial role on decreased MDA levels and increased antioxidant function in the skeletal muscle of rat fed a high fat diet.

• International Journal of Industrial Entomology and Biomaterials
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• v.13 no.1
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• pp.23-30
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• 2006

BmCu/Zn SOD was isolated from early embryo of Bombyx mori using microarray analysis. The BmCu/Zn SOD gene was observed during the early embryonic stage with the strongest signal found at the unfertilizaion, fertilization and blastoderm stages. The BmCu/Zn SOD gene encodes a protein of 154 amino acids with a calculated Mr of 15 kDa. The deduced amino acid sequence of BmCu/Zn SOD indicated that the residues that form on the Cu/Zn binding site are conserved and that the sequence is a 60% identity to that of M. domestica. In a phylogenetic tree, Bm SOD was also close to Drosophila SODs rather than other insect SODs. The BmCu/Zn SOD gene exists as a single copy in the genome. Transcripts of BmCu/Zn SOD cDNA were identified by northern blot analysis. The expression of the BmCu/Zn SOD gene was observed weakly in most of larvae, pre-pupae, pupae and adult tissues. Also, the BmCu/Zn SOD gene was observed in early embryonic stage. Although the roles of SODs remains to be further elucidated, the high expression of BmCu/Zn SOD gene at before 24 h post fertilization suggests that this gene is of general importance during early embryogenesis in the Bombyx mod.

• BMB Reports
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• v.38 no.1
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• pp.111-114
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• 2005

Heat shock proteins (HSPs) are known to protect cells from oxidative stress and other types of injuries. We previously reported the neuroprotective effect of HSP70 following cerebral ischemia and reperfusion using hsp 70.1 knockout (KO) mice. However, the precise role of HSP70 in neuroprotection has not been established yet. The purpose of this study was to investigate the relationship between HSP70 and antioxidant enzymes using hsp 70.1 KO mice. The activities of both SOD-1 and SOD-2 were significantly decreased in hsp 70.1 KO mice than in the wild type (WT) littermates. SOD-1 protein level in the hsp 70.1 KO mice was lower than that of WT. We speculate that HSP70 might be involved in regulation of expression of SOD-1 at the level of transcription or by post-transcriptional modification.

• Journal of Life Science
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• v.20 no.4
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• pp.555-560
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• 2010

The objective of this study was to investigate levels of serum creatinine, CuSOD and MnSOD protein expression in the kidney after renal ischemic reperfusion with pre-exercise using heat shock protein 70.1 in knock-out mice (KO). The C57/BL6 strain (Wild type: WT) and KO were divided into 4 groups as follows: Sham control group (Sham), pre-exercise group (Ex), pre-exercise +ischemia group (Ex+IR), and ischemia group (IR). CuSOD and MnSOD expression were significantly decreased (p<0.01, p<0.05) and blood creatinine concentration was significantly increased (p<0.01) in the IR group of KO. In contrast, CuSOD and MnSOD expression in the Ex+IR group of KO were higher than the IR group, while creatinine concentration was significantly lower. These results suggest that Hsp70 is directly correlated to renal ischemic reperfusion injury. Pre-exercise in renal ischemia might prevent or inhibit positive oxidative stress inhibitory effects by increasing anti-oxidative enzymes (CuSOD, MnSOD) within the kidney and improve to prevent renal function. Thus, pre-exercise may have a protective role against renal injury after renal ischemia.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.522-534
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• 1995

Background: In the pathogenesis of acute lung injury induced by lipopolysaccharide(LPS), oxygen radiclls are known to be involved in one part. Superoxide dismutase(SOD) protects oxygen radical-induced tissue damage by dismutating superoxide to hydrogen peroxide. In eukaryotic cells, two forms of SOD exist intracellularly as a cytosolic, dimeric copper/zinc-containing SOD(CuZnSOD) and a mitochondrial, tetrameric manganese-containing SOD(MnSOD). But there has been little information about SOD gene expression and its regulation in pulmonary alveolar macrophages(PAMs). The objective of this study is to evaluate the SOD gene expression induced by LPS and its regulation in PAMs of rat. Method: In Sprague-Dawley rats, PAMs obtained by broncholaveolar lavage were purified by adherence to plastic plate. To study the effect of LPS on the SOD gene expression of PAMs, they were stimulated with different doses of LPS($0.01{\mu}g/ml{\sim}10{\mu}g/ml$) and for different intervals(0, 2, 4, 8, 24hrs). Also for evaluating the level of SOD gene regulation actinomycin D(AD) or cycloheximide(CHX) were added respectively. To assess whether LPS altered SOD mRNA stability, the rate of mRNA decay was determined in control group and LPS-treated group. Total cellular RNA extraction by guanidinium thiocyanate/phenolfchlorofonn method and Northern blot analysis by using a $^{32}P$-labelled rat MnSOD and CuZnSOD cDNAs were performed. Results: The expression of mRNA in MnSOD increased dose-dependently, but not in CuZnSOD. MnSOD mRNA expression peaked at 8 hours after LPS treatment. Upregulation of MnSOD mRNA expression induced by LPS was suppressed by adding AD or CHX respectively. MnSOD mRNA stability was not altered by LPS. Conclusion: These findings show that PAMs of rat could be an important source of SOD in response to LPS, and suggest that their MnSOD mRNA expression may be regulated transcriptionally and require de novo protein synthesis without affecting mRNA stability.

• Fisheries and Aquatic Sciences
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• v.12 no.3
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• pp.179-184
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• 2009

Hemibarbus mylodon (Cypriniformes) is an endemic freshwater fish species in the Korean peninsula, for which urgent conservation efforts are needed. To understand their stress responses in relation to metal toxicity and thermal elevation, we performed a real-time RT-PCR-based expression assay of hepatic copper/zinc-superoxide dismutase (Cu/Zn-SOD), a key antioxidant enzyme, in response to experimental heavy metal exposure or heat treatment. The transcription of hepatic Cu/Zn-SOD was differentially modulated by acute exposure to Cu, cadmium (Cd), or Zn. Exposure to each metal at $5{\mu}M$ for 24 h revealed that Cu stimulated the mRNA expression of Cu/Zn-SOD to a greater extent than the other two heavy metals. The elevation in Cu/Zn-SOD transcripts in response to Cu exposure was dose-dependent (0.5 to $5{\mu}M$). Time course analysis of Cu/Zn-SOD expression in response to Cd exposure ($5{\mu}M$) revealed a transient pattern up to day 7. Exposure to thermal stress (an increase from 22 to $30^{\circ}C$ at a rate of $1^{\circ}C/h$ followed by $30^{\circ}C$ for 18 h) did not significantly alter SOD transcription, although heat shock protein 90 kDa (HSP90) transcription was positively correlated with an increase in temperature.

• Toxicological Research
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• v.28 no.1
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• pp.19-24
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• 2012

In the present study, toxicity of silver nanoparticles (AgNPs) was investigated in the nematode, Caenohabditis elegans focusing on the upstream signaling pathway responsible for regulating oxidative stress, such as mitogen-activated protein kinase (MAPK) cascades. Formation of reactive oxygen species (ROS) was observed in AgNPs exposed C.elegans, suggesting oxidative stress as an important mechanism in the toxicity of AgNPs towards C. elegans. Expression of genes in MAPK signaling pathways increased by AgNPs exposure in less than 2-fold compared to the control in wildtype C.elegans, however, those were increased dramatically in sod-3 (gk235) mutant after 48 h exposure of AgNPs (i.e. 4-fold for jnk-1 and mpk-2; 6-fold for nsy-1, sek-1, and pmk-1, and 10-fold for jkk-1). These results on the expression of oxidative stress response genes suggest that sod-3 gene expression appears to be dependent on p38 MAPK activation. The high expressions of the pmk-1 gene 48 h exposure to AgNPs in the sod-3 (gk235) mutant can also be interpreted as compensatory mechanisms in the absence of important stress response genes. Overall results suggest that MAPK-based integrated stress signaling network seems to be involved in defense to AgNPs exposure in C.elegans.

• BMB Reports
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• v.44 no.7
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• pp.462-467
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• 2011

Up-regulation of selected matrix metalloproteinases (MMPs) such as MMP-9 contributes to inflammatory processes during the development of various skin diseases, such as atopic dermatitis. In this study, we examined the effect of a cell-permeable superoxide dismutase (Tat-SOD) on TNF-${\alpha}$-induced MMP-9 expression in human keratinocyte cells (HaCaT). When Tat-SOD was added to the culture medium of HaCaT cells, it rapidly entered the cells in dose- and time-dependent manners. Tat-SOD decreased TNF-${\alpha}$-induced reactive oxygen species (ROS) generation. Tat-SOD also inhibited TNF-${\alpha}$-induced NF-${\kappa}B$ DNA binding activity. Treatment of HaCaT cells with Tat-SOD significantly inhibited TNF-${\alpha}$-induced mRNA and protein expression of MMP-9, as measured by RT-PCR and Western blot analysis. In addition, Tat-SOD suppressed TNF-${\alpha}$-induced gelatinolytic activity of MMP-9. Taken together, our results indicate that Tat-SOD can suppress TNF-${\alpha}$-induced MMP-9 expression via ROS-NF-${\kappa}B$-dependent mechanisms in keratinocytes, and therefore can be used as an immunomodulatory agent against inflammatory skin diseases related to oxidative stress.