• 제목/요약/키워드: Paraoxonase 2

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PROTECTION OF PARAOXONASE BY LIPIDS

  • Su, Nguyen-Duy;Kim, Ju-Ruyng;Sok, Dai-Eun
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.219.2-220
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    • 2003
  • Effect of lipids on the oxidative inactivation of paraoxonasel (PON1), a HDL -associated antioxidant protein, was investigated, based on the hydrolysis of phenyl acetate. First. various fatty acids were examined for the prevention against the inactivation of PON1 byascorbate/Cu2+ system, which caused a remarkable ($\geq$ 90%) inactivation of PON1, accompanied by a partial loss of histidine residues. (omitted)

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한우에서 임신 초기 발현 차이 혈장 단백질의 단백질체학적 분석 (Proteomic Analysis of Differentially Expressed Plasma Proteins during Early Pregnancy in Hanwoo)

  • 김평희;권대진;오건봉;이휘철;양병철;임기순;민관식;윤종택;진동일;박수봉;황성수
    • Reproductive and Developmental Biology
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    • 제34권3호
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    • pp.235-240
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    • 2010
  • This study was performed to comprehend the plasma proteins expressed specifically during early pregnancy in pregnant or non-pregnant Hanwoo using proteomic analysis technique. Plasma samples (0, 2, 3, 4, 7, and 11 weeks after AI) were obtained from pregnant (P, n=3) or non-pregnant (NP, n=4) Hanwoo, respectively. To evaluate proteins differentially expressed, 2-dimensional electrophoresis (2DE) was conducted. Normalized protein spots were selected for the significant expression variation deviated over two fold in its expression level between two groups; Molecular functions of the proteins were DNA binding, protein binding, hemoglobin binding, ferrochelatase and transporter activity and arylestera, respectively. According to western blotting, haptoglobin was specifically expressed only in NP group during early pregnancy; however, paraoxonase 1 was highly expressed in pregnant group. Based on these results, pregnancy was maintained successfully by the activation of specific plasma proteins associated with immune system and antioxidant regulation during early pregnancy in Hanwoo.

Engineered Recombinant PON1-OPH Fusion Hybrids: Potentially Effective Catalytic Bioscavengers against Organophosphorus Nerve Agent Analogs

  • Lee, Nari;Yun, Hyeongseok;Lee, Chan;Lee, Yikjae;Kim, Euna;Kim, Sumi;Jeon, Hyoeun;Yu, Chiho;Rho, Jaerang
    • Journal of Microbiology and Biotechnology
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    • 제31권1호
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    • pp.144-153
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    • 2021
  • Organophosphorus nerve agents (OPNAs), including both G- and V-type nerve agents such as sarin, soman, tabun and VX, are extremely neurotoxic organophosphorus compounds. Catalytic bioscavengers capable of hydrolyzing OPNAs are under development because of the low protective effects and adverse side effects of chemical antidotes to OPNA poisoning. However, these bioscavengers have certain limitations for practical application, including low catalytic activity and narrow specificity. In this study, we generated a fusion-hybrid form of engineered recombinant human paraoxonase 1 (rePON1) and bacterial organophosphorus hydrolase (OPH), referred to as GV-hybrids, using a flexible linker to develop more promising catalytic bioscavengers against a broad range of OPNAs. These GV-hybrids were able to synergistically hydrolyze both G-type OPNA analogs (paraoxon: 1.7 ~ 193.7-fold, p-nitrophenyl diphenyl phosphate (PNPDPP): 2.3 ~ 33.0-fold and diisopropyl fluorophosphates (DFP): 1.4 ~ 22.8-fold) and V-type OPNA analogs (demeton-S-methyl (DSM): 1.9 ~ 34.6-fold and malathion: 1.1 ~ 4.2-fold above) better than their individual enzyme forms. Among the GV-hybrid clones, the GV7 clone showed remarkable improvements in the catalytic activity toward both G-type OPNA analogs (kcat/Km (106 M-1 min-1): 59.8 ± 0.06 (paraoxon), 5.2 ± 0.02 (PNPDPP) and 47.0 ± 6.0 (DFP)) and V-type OPNA analogs (kcat/Km (M-1 min-1): 504.3 ± 48.5 (DSM) and 1324.0 ± 47.5 (malathion)). In conclusion, we developed GV-hybrid forms of rePON1 and bacterial OPH mutants as effective and suitable catalytic bioscavengers to hydrolyze a broad range of OPNA analogs.

Transcriptional activation of an anti-oxidant mouse Pon2 gene by dexamethasone

  • Lim, Ji-Ae;Kim, Sang-Hoon
    • BMB Reports
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    • 제42권7호
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    • pp.421-426
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    • 2009
  • Glucocorticoids regulate multiple physiological processes such as metabolic homeostasis and immune response. Mouse Pon2 (mPon2) acts as an antioxidant to reduce cellular oxidative stress in cells. In this present study, we investigated the transcriptional regulation of mPon2 by glucocorticoids. In the presence of glucocorticoid analogue dexamethasone, the expression of mPon2 mRNA in cells was increased, whereas the expression was inhibited by a transcription inhibitor actinomycin D. Glucocorticoid receptors bound to the putative glucocorticoid response elements located between -593 bp and -575 bp of the mPon2 promoter. Transcriptional activity was completely blocked when the putative element was mutated. Taken together, these results suggest that the expression of the mPon2 gene is directly regulated by glucocorticoid-glucocorticoid receptor complexes.

Paraoxonase 1 (PON1) Q192R Gene Polymorphism and Cancer Risk: A Meta-Analysis Based on 30 Publications

  • Zhang, Meng;Xiong, Hu;Fang, Lu;Lu, Wei;Wu, Xun;Huang, Zhan-Sen;Wang, Yong-Qiang;Cai, Zhi-Ming;Wu, Song
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권10호
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    • pp.4457-4463
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    • 2015
  • Common genetic variation Q192R in the paraoxonase 1 (PON1) gene has been considered to be implicated in the development of many cancers. Nevertheless, results from the related studies were inconsistent. To elucidate the association, we performed a meta-analysis for 8,112 cases and 10,037 controls from 32 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association by STATA 12.0 software. Overall, we revealed that the PON1-192R allele was associated with a reduced risk of the overall cancers. Moreover, in the stratified analysis by cancer types (breast cancer, prostate cancer, brain cancer etc.), the results showed that PON1-192R allele was associated with a decreased risk in breast cancer (R vs Q: OR=0.605, 95% CI=0.378-0.967, $P_{heterogeneity}=0.000$; RR vs QQ: OR=0.494, 95% CI=0.275-0.888, $P_{heterogeneity}=0.002$; RQ vs QQ: OR=0.465, 95% CI=0.259-0.835, $P_{heterogeneity}=0.000$; and RR+RQ vs QQ: OR=0.485, 95% CI=0.274-0.857, $P_{heterogeneity}=0.000$), and associated with prostate cancer in homozygote (RR vs QQ: OR=0.475, 95% CI=0.251-0.897, $P_{heterogeneity}=0.001$) and recessive models (RR vs RQ+QQ: OR=0.379, 95% CI=0.169-0.853, $P_{heterogeneity}=0.000$), while an increased risk was identified in lymphoma (R vs Q: OR=1.537, 95% CI=1.246-1.896, $P_{heterogeneity}=0.944$; RR vs QQ: OR=2.987, 95% CI=1.861-4.795, $P_{heterogeneity}=0.350$; RR+RQ vs QQ: OR=1.354, 95% CI=1.021-1.796, $P_{heterogeneity}=0.824$; and RR vs RQ+QQ: OR=2.934, 95% CI=1.869-4.605, $P_{heterogeneity}=0.433$), and an increased risk in prostate cancer under heterozygote comparison (RQ vs QQ: OR=1.782, 95% CI=1.077-2.950, $P_{heterogeneity}=0.000$) and dominant models (RR+RQ vs QQ: OR=1.281, 95% CI=1.044-1.573, $P_{heterogeneity}=0.056$). When subgroup analysis that performed by the control source (hospital based or population based), a decreased risk of the overall cancers was revealed by homozygote (RR vs QQ: OR=0.601, 95% CI=0.366-0.987, $P_{heterogeneity}=0.000$) and dominant models (RR vs RQ+QQ: OR= 0.611, 95% CI=0.384-0.973, $P_{heterogeneity}=0.000$) in hospital based group. Stratifying by ethnicity, a significantly reduced risk of the overall cancers under allele contrast model (R vs Q: OR=0.788, 95% CI=0.626-0.993, $P_{heterogeneity}=0.000$) was uncovered in Caucasian. In summary, these findings suggested that PON1 Q192R polymorphism was associated with a reduced risk of the overall cancers, nevertheless, it might increase cancer susceptibility of prostate and lymphoma risk. Large well-designed epidemiological studies will be continued on this issue of interest.

Severely modified lipoprotein properties without a change in cholesteryl ester transfer protein activity in patients with acute renal failure secondary to Hantaan virus infection

  • Kim, Ji-Hoe;Park, Hyun-Ho;Choi, In-Ho;Kim, Young-Ok;Cho, Kyung-Hyun
    • BMB Reports
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    • 제43권8호
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    • pp.535-540
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    • 2010
  • Patients with hemorrhagic fever with renal syndrome (HFRS) often exhibit altered serum lipid and lipoprotein profile during the oliguric phase of the disease. Serum lipid and lipoprotein profiles were assessed during the oliguric and recovery phases in six male patients with HFRS. In the oliguric phase of HFRS, the apolipoprotein (apo) C-III content in high-density lipoproteins (HDL) was elevated, whereas the apoA-I content was lowered. The level of expression and activity of antioxidant enzymes were severely reduced during the oliguric phase, while the cholesteryl ester transfer protein activity and protein level were unchanged between the phases. In the oliguric phase, electromobility of $HDL_2$ and $HDL_3$ was faster than in the recovery phase. Low-density lipoprotein (LDL) particle size was smaller and the distribution was less homogeneous. Patients with HFRS in the oliguric phase had severely modified lipoproteins in composition and metabolism.

Oxytocin Ameliorates Remote Liver Injury Induced by Renal Ischemia-Reperfusion in Rats

  • Hekimoglu, Askin Tas;Toprak, Gulten;Akkoc, Hasan;Evliyaoglu, Osman;Ozekinci, Selver;Kelle, Ilker
    • The Korean Journal of Physiology and Pharmacology
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    • 제17권2호
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    • pp.169-173
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    • 2013
  • Renal ischemia-reperfusion (IR) causes remote liver damage. Oxytocin has anti-inflammatory and antioxidant effects. The main purpose of this study was to evaluate the protective function of oxytocin (OT) in remote liver damage triggered by renal IR in rats. Twenty four rats were randomly divided into four different groups, each containing 8 rats. The groups were as follows: (1) Sham operated group; (2) Sham operated+OT group (3) Renal IR group; (4) Renal IR+OT group. OT ($500{\mu}g/kg$) was administered subcutaneously 12 and 24 hours before and immediately after ischemia. At the end of experimental procedure, the rats were sacrificed, and liver specimens were taken for histological assessment or determination of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), paraoxonase (PON-1) activity and nitric oxide (NO). The results showed that renal IR injury constituted a notable elevation in MDA, TOS, Oxidative stress index (OSI) and significantly decreased TAS, PON-1 actvity and NO in liver tissue (p<0.05). Additionally renal IR provoked significant augmentation in hepatic microscopic damage scores. However, alterations in these biochemical and histopathological indices due to IR injury were attenuated by OT treatment (p<0.05). These findings show that OT ameliorates remote liver damage triggered by renal ischemia-reperfusion and this preservation involves suppression of inflammation and regulation of oxidant-antioxidant status.

폐경 후 여성에서 이소플라본과 감마 리놀렌산의 보충 섭취가 혈중 지질 농도 및 갱년기 증상에 미치는 영향 (The Effect of Isoflavone and Gamma-linolenic Acid Supplementation on Serum Lipids and Menopausal Symptoms in Postmenopausal Women)

  • 곽정현;김지영;김혜진;신동혁;이종호
    • Journal of Nutrition and Health
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    • 제43권2호
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    • pp.123-131
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    • 2010
  • 본 연구 결과를 요약하면 다음과 같다. 1) 산화 LDL 농도는 이소플라본 및 감마 리놀렌산 보충군에서 유의적으로 감소 (p = 0.006), 플라시보군에서 유의적인 변화 없었음. 두 군간 비교에서 유의적인 차이가 있었음 (p = 0.011). 2) 혈청에서의 중성지방, 총 콜레스테롤, LDL 콜레스테롤, HDL 콜레스테롤, 아포지단백 A1, B 등의 농도는 두 군에서 모두 유의적인 차이가 없었음. 3) LDL particle size와 Paraoxonase 활성도는 두 군에서 모두 유의적인 차이가 없었음. 지질과산화지표인 혈장 MDA 농도는 두 군간 변화량 비교에서만 유의적인 차이가 있었음 (p = 0.010). 4) 갱년기 증상 지표인 Modified kupperman index (KI)는 이소플라본 및 감마 리놀렌산 보충군과 플라시보군에서 모두 유의적으로 감소하였음 (p < 0.001). KI 수치의 군간 비교에서는 유의적인 차이가 없었음. 이소플라본 및 감마 리놀렌산 복합제재를 12주간 섭취하였을 때 이소플라본 및 감마 리놀렌산 보충군에서 산화 LDL 농도가 유의적인 감소하였고, 두 군간의 비교시 MDA 농도 변화량의 유의적인 차이를 확인하였다. 이소플라본 및 감마리놀렌산 복합제재 섭취는 산화적 스트레스로부터 체내 LDL-콜레스테롤의 산화를 예방하는데 도움을 줄 수 있을 것으로 사료된다. 우리나라에서 폐경 후 여성을 대상으로 이소플라본 및 감마리놀렌산 복합 제재 섭취와 관련 된 연구는 매우 미흡한 실정임으로 복합제재의 용량 설정을 세분화 하고 복용기간을 연장한 후속 연구가 필요할 것으로 사료된다.

스피루리나 첨가 샐러드 드레싱 보충 식이가 마우스 혈장 항산화 지표 및 DNA보호에 미치는 영양 (Effects of Spirulina Added Salad Dressing on the Antioxidant Index and DNA Protection in Mice)

  • 양윤형;조흔;패넬로프 펠리프;이정희;이선영;조용식;전혜경;송경빈;김미리
    • 동아시아식생활학회지
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    • 제15권4호
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    • pp.386-396
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    • 2005
  • The effects of spirulina-added salad dressing on lipid profiles and antioxidant biomarkers such as total glutathionine, TBARS value, carbonyl value, GPx, GR, SOD and paraoxonase activity in plasma or liver of mice were evaluated Sixteen male ICR mice weighing 20$\pm$2 g were divided into two groups and fed low fat ($5\%$ fat) diet (low fat control: LFC) and low fat control plus dressing diet (LFD) for eight weeks. Body weight, tissue weights of liver, heart and kidney, and the distribution of body fat deposition were not significantly different between two groups. Also, the profile of TG, TC, LDL and HDL cholesterol were similar between two groups. The DNA damage was determined using the comet assay (single cell gel assay) with alkaline electrophoresis and quantified by measuring tail length (TL). Spirulina salad dressing consumption resulted in significant decrease in lymphocyte DNA damage expressed by TL (LFC: $28.8{\mu}m$, LFD: $20.3{\mu}m$). Additionally, salad dressing consumption for 8 wks decreased the lipid peroxidation assayed by TBARS to $12.6\%$ compared with the control. The levels of antioxidant vitamins such as $\beta$-carotene were significantly higher in plasma of LFD group than those in LFC group based on HPLC method This study shows that spirulina-added salad dressing exerts degenerative disease-protective effects on oxidative DNA damage and lipid peroxidation possibly via a free radical levels.

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