• Environmental Analysis Health and Toxicology
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• v.20 no.4 s.51
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• pp.287-296
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• 2005

아연은 다양한 독성 물질로부터 유도된 아폼토시스를 저해하는 것으로 알려져 있으나 이 기전에 대해서는 명확히 밝혀지지 않았다. 본 연구에서는 인간 유방암 세포 MCF-7에 카드뮴을 처리하였을 때 유도되는 아폼토시스에 대한 아연의 저해효과를 살펴보았다. 아연의 아폼토시스 저해 효과는 DNA분절현상, 핵의 쪼개짐 그리고 caspase-9의 발현을 통하여 확인하였다. 또한 아연의 아폼토시스 저해효과가 카드뮴에 의한 산화적 스트레스와 관련이 있는지 확인하기 위하여 활성산소인 peroxide의 농도를 세포내에서 측정하였다. 나아가 superoxide dismutase (SOD), catalase (CAT) 그리고 glutahion redurtase (CR)같은 활성산소에 대한 인체내 방어기작으로 작용하는 항산화 효소의 활성을 측정하였다. 본 연구를 통해 아연이 카드뮴에 의해 생성된 세포내의 활성산소의 양을 감소시키고 항산화 효소를 회복시키는 기전이 카드뮴에 의한 아폼토시스를 저해하는 한 요인으로 사료되어진다.

• Clinical and Experimental Pediatrics
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• v.62 no.12
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• pp.444-449
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• 2019

Background: Sixty percent of infants with severe neonatal hypoxic-ischemic encephalopathy die, while most survivors have permanent disabilities. Treatment for neonatal hypoxic-ischemic encephalopathy is limited to therapeutic hypothermia, but it does not offer complete protection. Here, we investigated whether hypoxia-inducible factor (HIF) promotes cell survival and suggested neuroprotective strategies. Purpose: HIF-1α deficient mice have increased brain injury after neonatal hypoxia-ischemia (HI), and the role of HIF-2α in HI is not well characterized. Copper-zinc superoxide dismutase (SOD)1 overexpression is not beneficial in neonatal HI. The expression of HIF-1α and HIF-2α was measured in SOD1 overexpressing mice and compared to wild-type littermates to see if alteration in expression explains this lack of benefit. Methods: On postnatal day 9, C57Bl/6 mice were subjected to HI, and protein expression was measured by western blotting in the ipsilateral cortex of wild-type and SOD1 overexpressing mice to quantify HIF-1α and HIF-2α. Spectrin expression was also measured to characterize the mechanism of cell death. Results: HIF-1α protein expression did not significantly change after HI injury in the SOD1 overexpressing or wild-type mouse cortex. However, HIF-2α protein expression increased 30 minutes after HI injury in the wild-type and SOD1 overexpressing mouse cortex and decreased to baseline value at 24 hours after HI injury. Spectrin 145/150 expression did not significantly change after HI injury in the SOD1 overexpressing or wild-type mouse cortex. However, spectrin 120 expression increased in both wild-type and SOD1 overexpressing mouse at 4 hours after HI, which decreased by 24 hours, indicating a greater role of apoptotic cell death. Conclusion: HIF-1α and HIF-2α may promote cell survival in neonatal HI in a cell-specific and regional fashion. Our findings suggest that early HIF-2α upregulation precedes apoptotic cell death and limits necrotic cell death. However, the influence of SOD was not clarified; it remains an intriguing factor in neonatal HI.

• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.215-221
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• 1994

Background: It is well known that oxygen free radicals(OFR) play a vital role in the various type of acute lung injury. Among various antioxidant defense mechanisms, the superoxide dismutases(SOD) are thought to be the first line of antioxidant defense by catalyzing the dismutation of two superoxide radicals to yield hydrogen peroxide and oxygen. Eukaryotic cells contain two types of intracellular SOD : cytosolic, dimeric copper/zinc- containing enzyme(CuZnSOD) and mitochondrial, tetrameric manganese-containing enzyme(MnSOD). The purpose of this study is to evaluate the time-dependent gene expression of MnSOD and CuZnSOD in the endotoxin-treated rats, and to compare with the manifestations of LPS-induced acute lung injury in rats. Methods: Total RNA from rat lung was isolated using single step phenol extraction 0, 1, 2, 4, 6, 12, 18, 24 hours after E. coli endotoxin injection(n=3, respectively). RNA was separated by formaldehyde-containing 1.2% agarose gels elctrophoresis, transblotted, baked, prehybridized, and hybridized with $^{32}P$-labeled cDNA probes for rat MnSOD and CuZnSOD, which were kindly donated by Dr. Ho(Duke University, Durham, NC, USA). The probes were labeled by nick translation. Blots were washed and autoradiography were quantitated using laser densitometry. Equivalent amounts of total RNA/gel were assessed by monitoring 28S and 18S rRNA. Results: Endotoxin caused a rise in steady-state MnSOD mRNA levels by 4h with peak mRNA accumulation by 6h. Continued MnSOD mRNA expression was observed at 12h. CuZnSOD mRNA expression was observed from 1h to 24h with peak levels by 18h. Conclusion: These results suggest that SOD palys an important defensive role in the endotoxin-induced acute lung injury in rats.

• Korean Journal of Veterinary Research
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• v.55 no.2
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• pp.133-139
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• 2015

The increasing uses of zinc oxide nanoparticles (nZnO) in industrial and personal care products raise possible danger of using nZnO in human. To determine whether ZnO induces size-dependent anomalies during embryonic organogenesis, mouse embryos on embryonic day 8.5 were cultured for 2 days under 50, 100, and $150{\mu}g$ of nZnO (< 100 nm) or micro-sized ZnO (mZnO; $80{\pm}25{\mu}m$), after which the morphological changes, cumulative quantity of Zn particles, and expressions of antioxidant and apoptotic genes were investigated. Although embryos exposed to $50{\mu}g$ of ZnO exhibited no defects on organogenesis, embryos exposed to over $100{\mu}g$ of ZnO showed increasing anomalies. Embryos treated with $150{\mu}g$ of nZnO revealed significant changes in Zn absorption level and morphological parameters including yolk sac diameter, head length, flexion, hindbrain, forebrain, branchial bars, maxillary process, mandibular process, forelimb, and total score compared to the same dose of mZnO-treated embryos. Furthermore, CuZn-superoxide dismutase, cytoplasmic glutathione peroxidase (GPx) and phospholipid hydroperoxidase GPx mRNA levels were significantly decreased, but caspase-3 mRNA level was greatly increased in nZnO-treated embryos as compared to normal control embryos. These findings indicate that nZnO has severer teratogenic effects than mZnO in developing embryos.

• 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.

• Journal of Nutrition and Health
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• v.41 no.8
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• pp.691-700
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• 2008

One suggested mechanism underlying copper (Cu) deficiency teratogenicity is a low availability of nitric oxide (NO), signaling molecule which is essential in developmental processes. Increased superoxide anions secondary to decreased activities of Cu-zinc superoxide dismutase (Cu-Zn SOD) in Cu deficiency can interact with NO to form peroxynitrite, which can nitrate proteins at tyrosine residues. In addition, peroxynitrite formation can limit NO bioavailability. We previously reported low NO availability and increased protein nitration in Cu deficient (Cu-) embryos. In the current study, we tested whether Cu deficiency alters downstream signaling of NO by assessing cyclic GMP (cGMP) and phosphorylated vasodilator-stimulating phosphoprotein (VASP) levels, and whether NO supplementation can affect these targets as well as protein nitration. Gestation day 8.5 embryos from Cu adequate (Cu+) or Cu- dams were collected and cultured in either Cu+ or Cu- media for 48 hr. A subset of embryos was cultured in Cu- media supplemented with a NO donor (DETA/NONOate; 20 ${\mu}M$) and/or Cu-Zn SOD. Cu-/Cu- embryos showed a higher incidence of embryonic and yolk sac abnormalities, low NO availability, blunted dose-response in NO concentrations to increasing doses of acetylcholine, low mRNA expression of endothelial nitric oxide synthase (eNOS), increased levels of 3-nitrotyrosine (3-NT) compared to Cu+/Cu+ controls. cGMP concentrations tended to be low in Cu-/Cu- embryos, and they were significantly lower in Cu-/Cu- yolk sacs than in controls. Levels of phosphorylated VASP at serine 239 (P-VASP) were similar in all groups. NO donor supplementation to the Cu- media ameliorated embryonic and yolk sac abnormalities, and resulted in increased levels of cGMP without altering levels of P-VASP and 3-NT. Taken together, these data support the concept that Cu deficiency limits NO availability and alters NO/cGMP-dependent signaling in Cu- embryos and yolk sacs, which contributes to Cu deficiency-induced abnormal development.

• Journal of Animal Science and Technology
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• v.64 no.1
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• pp.70-83
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• 2022

A set of studies was performed to determine the influence of dietary ZnO concentration and source during two phases (days 0 to 14 and days 15 to 28). Experiment 1: 168 weaned piglets were allocated to four treatment groups in six replicates. The treatments included a basal diet without ZnO supplementation (control), 2,500 mg ZnO/kg (In2500), 500 mg nano-ZnO/kg (N500), and 150 mg nano-ZnO/kg (N150). Experiment 2: 168 weaned piglets were divided into three treatment groups with eight replicates. The treatments included control, In2500, N300, and 150 mg nano-ZnO/kg (N150). An in vitro trial showed that the growth of Listeria monocytogenes, Escherichia coli, and Salmonella typhimurium was inhibited when exposed to 300 and 500 ppm of ZnO after 24 h of incubation. In experiment 1, the average daily gain (ADG) by the pigs was improved in the N500 and IN2500 treatment groups. Colonization of coliforms and Clostridium spp. significantly decreased in the pigs fed the N500 and IN2500 diets in phase 1. The total plasma antioxidant capacity was greater in the IN2500 and N500 treatment groups than in the control. Superoxide dismutase (SOD) activity was greater in pigs fed the IN2500 (phase 1) or the IN2500 and N500 (phase 2) diets than in the control and N150 treatment group. In experiment 2, pigs in the N300 treatment group showed a higher ADG and lower fecal score colonization of coliforms and Clostridium spp. compared with those in the N150 treatment group. In conclusion, nano-ZnO at a dose of 300 ppm showed the same growth as the pharmacological dose of Zn. This provides an option to the pharmacological dose.

• Korean Journal of Community Nutrition
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• v.12 no.4
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• pp.396-404
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• 2007

Increased oxidative stress contributes to the progression of atherosclerosis. We measured serum antioxidant mineral concentrations, capacities of serum antioxidant enzymes and fasting lipid profile in 97 male patients with coronary artery disease (CAD) and 21 male controls. Nutrient intake was assessed by the semi-quantitative food frequency method. CAD patients were divided into single-vessel disease (SVD, n=66) and multi-vessel disease (MVD, n = 31) groups on the coronary angiography. The ratio of serum LDL- to HDL-cholesterol elevated with an increasing number of diseased vessels compared to the control (control < SVD < MVD, p < 0.05). Patients with SVD and MVD had higher levels of serum lipoprotein (a) than the control (p < 0.05). The mean intake of carbohydrate, protein and cholesterol was higher in MVD patients and the intakes of vitamins C and E were lower in MVD and SVD patients than in the control (p < 0.05). Serum copper (Cu) and zinc (Zn) levels were higher in MVD and SVD patients than in the control (Cu: control $75.8{\pm}5.07$, SVD $99.2{\pm}2.90$, MVD $100.1{\pm}2.32{\mu}g/dL$, p<0.01; Zn: $76.8{\pm}5.36$, $119.0{\pm}5.95$, $129.1{\pm}2.70{\mu}g/dL$, p < 0.01). And the ratio of Zn to Cu was higher in SVD and MVD patients than in the control (control $0.78{\pm}0.06$, SVD $0.88{\pm}0.05$, MVD $0.99{\pm}0.04$, P < 0.05). The activity of glutathione peroxidase (GSH-Px) was lower in MVD than in SVD and the control (control $35.13{\pm}1.34$, SVD $35.30{\pm}1.01$, MVD $31.00{\pm}1.04 U/mg$ protein, p < 0.05). The ratio of the activities of superoxide dismutase (SOD) to GSH-Px was higher in MVD than in control and SVD (p < 0.05). In groups with CAD, serum Cu and Zn concentrations and their ratio were changed compared to the control. GSH-Px activity was decreased and the ratio of SOD to GSH-Px was increased in the patients with MVD. The balances between the activities of SOD and GSH-Px should also be considered a risk factor in CAD patients.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.8
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• pp.1066-1072
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• 2010

In this study, the effects of replacing inorganic copper, zinc and manganese with different levels of organic complexes of the same trace minerals on the lipid peroxidation and antioxidant defense systems in broilers were investigated. Two-hundred Ross-308 one-day-old broiler chickens were placed on controlled diets until 42 d of age. The experimental animals were divided into four groups comprising three experimental groups and one control group, each consisting of 50 chickens. All groups were also divided into five subgroups each containing 10 broiler chicks. The mineral content of the control group diet was controlled using a standard inorganic mineral premix with supplement levels and sources of trace minerals typical of commercial broiler diets according to the National Research Council (NRC) (containing 8 mg Cu as $CuSO_4$, 40 mg Zn as $ZnSO_4$, and 60 mg Mn as MnO, per kg). In the experimental diets, mineral premix was also comprised of inorganic formulations, except for those of Cu, Zn and Mn. Organically-complexed Cu, Zn, and Mn were separately added to the basal diet at 1/3 (L1), 2/3 (L2) and 3/3 (L3) levels with respect to the NRC recommendation, as Bioplex $Cu^{TM}$, Bioplex $Zn^{TM}$, Bioplex $Mn^{TM}$. At the end of the trial, the plasma Zn level significantly increased when the plasma Cu level significantly decreased (p<0.05) in chickens fed at 2/3 and 3/3 levels of organically complexed minerals. The liver trace mineral concentrations were significantly higher in chickens fed inorganic trace minerals in comparison to those fed organically-complexed minerals. The plasma malondialdehyde (MDA) level of experimental chickens was decreased in groups receiving levels of organic Cu, Zn and Mn in comparison to those fed inorganic forms (p<0.01). The erythrocyte superoxide dismutase (SOD) activity was higher in all groups receiving the organic mineral supplements in comparison to those fed inorganic forms (p<0.01). No differences were observed on either the erythrocyte catalase (CAT) activity or the plasma ceruloplasmin (Cp) levels, and the liver MDA levels and liver CAT and SOD activities in any of the groups that received the organic supplements of Cu, Zn, and Mn. It was concluded that supplementation of lower levels of organically-complexed copper, zinc, and manganese instead of their inorganic forms in diets had no negative effects on the antioxidant defense system in broilers.

• Journal of Nutrition and Health
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• v.40 no.2
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• pp.105-110
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• 2007

The study was designed to observe antioxidant activities of conjugated linoleic acid (CLA) by determining antioxidant enzyme protein levels [cytochrome P4502 El (CYP2E1), Copper, Zinc-superoxide dismutase (CuZn-SOD), glutathione peroxidase (CSH-Px), glutathione S-transferase (GST)] by Western blot analysis and the levels of ${\alpha}$-tocopherol and 2-thiobarbituric acid reactive substances (TBARS) in the liver of chronically ethanol-treated rats. Sixty Sprague Dawley male rats were divided into 3 groups (Control, EtOH, EtOH+CLA). All rats were fed Lieber-DeCarli liquid diet for 4 weeks by pair-feeding against the EtOH group. The liquid diet was supplemented with 1.77g CLA mixture per kg diet in the EtOH+CLA group. Isocaloric maltose dextrin was added in replace of 50g ethanol (36%kcal) for the Control group. Ethanol ingestion significantly increased the levels of CYP2E1 protein and TBARS, but significantly reduced CuZn-SOD protein level and increased GST protein level. There was no significant effect on the level of GSH-Px protein and ${\alpha}$-tocopherol in the liver by ethanol. CLA supplementation with ethanol significantly increased the levels of CuZn-SOD, GSH-Px and GST and also significantly attenuated TBARS level, whereas there was no significant effect on the levels of CYP2E1 protein and ${\alpha}$-tocopherol by CLA. Overall, the CLA supplemented to ethanol could significantly increase the levels of CuZn-SOD, GSH-Px and GST proteins and reduce the level of TBARS in the liver of chronically ethanol-treated rats.