• BMB Reports
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• v.48 no.2
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• pp.91-96
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• 2015

Cells express several antioxidant enzymes to scavenge reactive oxygen species (ROS) responsible for oxidative damages and various human diseases. Therefore, antioxidant enzymes are considered biomedicine candidates. Among them, extracellular superoxide dismutase (SOD3) had showed prominent efficacy against asthma and inflammation. Despite its advantages as a biomedicine, the difficulty in obtaining large quantity of active recombinant human SOD3 (rhSOD3) has limited its clinical applications. We found that a significant fraction of over-expressed rhSOD3 was composed of the inactive apo-enzyme and its potency against inflammation depended on the rate of metal incorporation. Also, purified rhSOD3 was unstable and lost its activity very quickly. Here, we suggest an ideal preparative method to express, purify, and store highly active rhSOD3. The enzymatic activity of rhSOD3 was maximized by incorporating metal ions into rhSOD3 after purification. Also, albumin or polyethylene glycol prevented rapid inactivation or degradation of rhSOD3 during preparative procedures and long-term storage.

• Journal of Nutrition and Health
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• v.38 no.5
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• pp.364-372
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• 2005

This study is designed to examine the effects of dietary supplementation with vitamin E and dehydroepiandrosterone (DHEA) on the formation of preneoplastic lesions in diethylnitrosamine (DEN) induced rat hepatocarcinogenesis. All Weaning male Sprague-Dawley rats were initiated by a single dose of DEN (200mg/kg body weight), subjected to two­thirds partial hepatectomy 3 weeks later and were sacrificed 8 weeks after DEN initiation. Two weeks after initiation, rats were fed Purina purified rodent diet 5053 (Ralston Purina Rat chow, USA) with $1.5\%$ (15,000 IU/kg diet) vitamin E, $0.5\%$ DHEA and both of those supplemented diet for 6 weeks. Placental glutathione S-transferase (GST-P) positive foci, the activities of catalase, total-glutathione peroxidase (GPx) , glutathione reductase (GR), glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS) contents were decreased significantly by vitaimin E supplement. On the other hand GST-P positive foci number, Cu/Zn-superoxide dismutase (SOD) and glucose 6-phosphatase (G6Pase) activities weren't changed by vitamin E supplement. It might suggest that protective effect of vitamin E against hepatocarcinogens is not involved in the formation of the GST-P positive foci but related to the expansion of that. It seemed that vitamin E supplement helped endogenous defense system in carcinogenesis by decreasing TBARS contents, $H_2O_2$, organic peroxides. Therefore, vitamin E seemed to protect cell from free radical damage in carcinogenesis. By DHEA supplement liver weight and liver/body ratio were increased, the area and number of GST-P positive foci, the activities of catalase, GR, total GPx, GST and the TBARS contents were decreased significantly. On the other hand Cu/Zn-SOD and G6Pase activities weren't changed by DHEA supplement. In hepatocarcinogenesis the activities of antioxidant enzymes weren't increased by DHEA supplement. DHEA did not increase the oxidative stress, while DHEA seems to have anticarcinogenic effect in rats hepatocarcinogenesis.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.581-588
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• 2016

Lonchocarpine is a phenylpropanoid compound isolated from Abrus precatorius that has anti-bacterial, anti-inflammatory, antiproliferative, and antiepileptic activities. In the present study, we investigated the antioxidant effects of lonchocarpine in brain glial cells and analyzed its molecular mechanisms. We found that lonchocarpine suppressed reactive oxygen species (ROS) production and cell death in hydrogen peroxide-treated primary astrocytes. In addition, lonchocarpine increased the expression of anti-oxidant enzymes, such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), and manganese superoxide dismutase (MnSOD), which are all under the control of Nrf2/antioxidant response element (ARE) signaling. Further, mechanistic studies showed that lonchocarpine increases the nuclear translocation and DNA binding of Nrf2 to ARE as well as ARE-mediated transcriptional activities. Moreover, lonchocarpine increased the phosphorylation of AMP-activated protein kinase (AMPK) and three types of mitogen-activated protein kinases (MAPKs). By treating astrocytes with each signaling pathway-specific inhibitor, AMPK, c-jun N-terminal protein kinase (JNK), and p38 MAPK were identified to be involved in lonchocarpine-induced HO-1 expression and ARE-mediated transcriptional activities. Therefore, lonchocarpine may be a potential therapeutic agent for neurode-generative diseases that are associated with oxidative stress.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.427-433
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• 2017

Previously, we demonstrated that galangin (3,5,7-trihydroxyflavone) protects human keratinocytes against ultraviolet B (UVB)-induced oxidative damage. In this study, we investigated the effect of galangin on induction of antioxidant enzymes involved in synthesis of reduced glutathione (GSH), and investigated the associated upstream signaling cascades. By activating nuclear factor-erythroid 2-related factor (Nrf2), galangin treatment significantly increased expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS). This activation of Nrf2 depended on extracellular signal-regulated kinases (ERKs) and protein kinase B (AKT) signaling. Inhibition of GSH in galangin-treated cells attenuated the protective effect of galangin against the deleterious effects of UVB. Our results reveal that galangin protects human keratinocytes by activating ERK/AKT-Nrf2, leading to elevated expression of GSH-synthesizing enzymes.

• The Journal of Korean Physical Therapy
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• v.22 no.3
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• pp.61-69
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• 2010

Purpose: This study was designed to investigate correlations between physical fitness, antioxidant enzymes (SOD, CAT, GPX), lipid peroxidation levels (MDA), lipid profiles, lactate levels and cardiovascular variables in an exercising group and a control group. Methods: Twelve healthy young males (Exercise group: 6, Controls: 6). All subjects took physical fitness tests and blood samples were collected while subjects were resting. Results: In the exercise group, there were several significant correlations: between back strength and SOD enzyme levels (r=0.82, p=0.04), back strength and MDA (r=0.94, p=0.00), agility and GPX (r=0.81, p=0.04), and balance and GPX (r=0.81, p=0.04). In the control group, there were significant correlations between: dominant grip strength and MDA (r=-0.84, p=0.03), and agility and GPX (r= -0.82, p=0.04). In the exercise group, there were no significant correlations between physical fitness factors, TC, TG, HDL-C and lactate levels. In the control group, there were significant correlations between: back strength and TG (r=0.88, p=0.01), and agility and HDL-C (r= -0.84, p=0.03). In the exercise group, there were significant correlations between: non-dominant grip strength and SBP (r=0.94, p=0.00), dominant grip strength and SBP (r=0.85, p=0.03), and power and SBP (r=0.82, p=0.04). In controls, there were significant correlations between: dominant grip strength and DBP (r=-0.85, p=0.03), muscular endurance and ST level (r=-0.93, p=0.00), and muscular endurance and HR (r=-0.88, p=0.01). Conclusion: That cardiovascular patients and controls who participated in regular exercise maintained their antioxidant capacity suggests that long-term physical activity can counteract the negative dysfunction that characterizes sedentary lifestyle, probably by maintaining plasma antioxidant defenses and thereby preventing oxidative stress.

• Toxicological Research
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• v.27 no.1
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• pp.25-29
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• 2011

The cytochrome P450 (P450, CYP) are the superfamily of heme-containing monooxygenase enzymes, found throughout all nature including mammals, plants, and microorganisms. Mammalian P450 enzymes are involved in oxidative metabolism of a wide range of endo- and exogenous chemicals. Especially P450s involved in drug metabolisms are important for drug efficacy and polymorphisms of P450s in individuals reflect differences of drug responses between people. To study the functional differences of CYP2A6, CYP2D6, and CYP4A11 variants, we cloned the four CYP2A6, three CYP2D6, and three CYP4A11 variants, which were found in Korean populations, in mammalian expression vector pcDNA by PCR and examined their expressions in COS-7 mammalian cells using immunoblots using P450 specific polyclonal antibodies. Three of four CYP2A6, two of three CYP4A11, and two of three CYP2D6 variants showed expressions in COS-7 cells but the relative levels of expressions are remarkably different in those of each variants. Our findings may help to study and explain the differences between functions of CYP variants and drug responses in Korean populations.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.9-21
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• 2015

Cancer, a serious public health problem in worldwide, results from an excessive and uncontrolled proliferation of the body cells without obvious physiological demands of organs. The gastrointestinal tract, including the esophagus, stomach and intestine, is a unique organ system. It has the highest cancer incidence and cancer-related mortality in the body and is influenceed by both genetic and environmental factors. Among the various chemical elements recognized in the nature, some of them including zinc, iron, cobalt, and copper have essential roles in the various biochemical and physiological processes, but only at low levels and others such as cadmium, lead, mercury, arsenic, and nickel are considered as threats for human health especially with chronic exposure at high levels. Cadmium, an environment contaminant, cannot be destroyed in nature. Through impairment of vitamin D metabolism in the kidney it causes nephrotoxicity and subsequently bone metabolism impairment and fragility. The major mechanisms involved in cadmium carcinogenesis could be related to the suppression of gene expression, inhibition of DNA damage repair, inhibition of apoptosis, and induction of oxidative stress. In addition, cadmium may act through aberrant DNA methylation. Cadmium affects multiple cellular processes, including signal transduction pathways, cell proliferation, differentiation, and apoptosis. Down-regulation of methyltransferases enzymes and reduction of DNA methylation have been stated as epigenetic effects of cadmium. Furthermore, increasing intracellular free calcium ion levels induces neuronal apoptosis in addition to other deleterious influence on the stability of the genome.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3805-3809
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• 2014

Background: In Mexico, breast cancer (BCa) is the leading type of cancer in women. Cytochrome P450 (CYP450) is a superfamily of major oxidative enzymes that metabolize carcinogens and many antineoplastic drugs. In addition, these enzymes have influence on tumor development and tumor response to therapy. In this report, we analyzed the protein expression in patients with BCa and in healthy women. Links with some clinic-pathological characteristic were also assessed. Materials and Methods: Immunohistochemical analyses were conducted on 48 sets of human breast tumors and normal breast tissues enrolled in Hospital Militar de Especialidades de la Mujer y Neonatologia and Hospital Central Militar, respectively, during the time period from 2010 to 2011. Informed consent was obtained from all participants. Statistical analysis was performed using ${\chi}^2$ or Fisher exact tests to estimate associations and the Mann Whitney U test for comparison of group means. Results: We found a significant CYP3A4 overexpression in BCa stroma and gland regions in comparison with healthy tissue. A significant association between protein expression with smoking, alcoholism and hormonal contraceptives use was also observed. Additionally, we observed estrogen receptor (ER) and progesterone receptor (PR) positive association in BCa. Conclusions: We suggest that CYP3A4 expression promotes BCa development and can be used in the prediction of tumor response to different treatments. One therapeutic approach may thus be to block CYP3A4 function.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.49 no.4
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• pp.445-453
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• 2016

Seahorse Hippocampus abdominalis a marine teleost fish, has long been used as one of the essential materials in traditional Chinese medicine. However, the uses of seahorse have been limited due to its high cost, despite its beneficial biological activities. Seahorse has not been widely explored for its biofunctional properties and active components. In the present study, the enzymatic hydrolysates of seahorse were prepared by using two digestive enzymes (trypsin and pepsin) and five food grade enzymes (neutrase, protamex, alcalase, kojizyme, and flavourzyme). The enzymatic hydrolysates indicated higher hydrolysis yields than its water extract. Among them, the distilled water-pepsin hydrolysate (DP) which was obtained by distilled water extraction followed by pepsin hydrolysis, showed the highest yield and protein content as well as the highest alkyl radical scavenging activity. Also, it provided protective effects against oxidative stress induced by AAPH in vero cell and zebrafish. Further fractionation based on the molecular weight was carried out to identify it’s active components, and < 5 kDa (less than 5 kDa) molecular weight fraction was confirmed to have the highest antioxidant activity. In conclusion, this study suggests that DP of seahorse has antioxidant properties, and might be a novel and useful material from the marine origin for healthy functional foods and cosmetics.

• Preventive Nutrition and Food Science
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• v.10 no.4
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• pp.340-343
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• 2005

Induction of NAD(P)H:(quinone-acceptor) oxidoreductase (QR) which promotes obligatory two electron reduction of quinones and prevents their participation in oxidative cycling and thereby the depletion of intracellular glutathione, has been used as a marker for chemopreventive agents. Induction of phase II enzyme is considered to be an important mechanism of cancer prevention. In our previous study, we assessed the quinone reductase QR-inducing activities of 216 kinds of medicinal herb extracts in cultured murine hepatoma cells, BPRc1 and hepalc1c7 cells. Among the 216 herbal extracts tested in that study, extracts from Chrysanthemum zawadskii showed significant induction of QR. In this study, we examined QR-inducing activity of solvent fractions of the herbal extract. The dichloromethane fraction of the herb showed the highest QR induction among the samples fractionated with four kinds of solvents with different polarity. The fraction also significantly induced the activity of glutathione S-transferase (GST), one of the major detoxifying enzymes, at $4{\mu}g/mL\;and\;2{\mu}g/mL$ in hepalc1c7 and BPRc1 cells, respectively. In conclusion, dichloromethane-soluble fraction of Chrysanthemum zawadskii which showed relatively strong induction of detoxifying enzymes merits further study to identify active components and evaluate their potential as cancer preventive agents.