• 한국산업보건학회지
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• 제11권2호
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• pp.111-117
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• 2001

A cross-sectional study was performed to evaluate associations between lead biomarkers, lead-related symptoms, and ${\delta}$-aminolevulinic acid dehydratase (ALAD) genotype among 598 lead workers and 144 control office workers in storage battery industries, secondary smelting and litharge making industries. Lead inhibits the second enzymes, ALAD, in the heme synthesis pathway. ALAD gene, which codes for one of three isozymic proteins (termed ALAD1-1, ALAD1-2, and ALAD2-2), seems to modify the toxicokinetics of lead. The result as follows; The percents of total workers whose genotype of ALAD1-1 and ALAD1-2 were 88.4% and 11.6%, respectively. The zinc protoporphyrin in blood (ZPP) and ${\delta}$-aminolevulinic acid in urine (ALAU) of lead workers with ALAD1-2 were significantly lower than those of lead workers with ALAD1-1, but there were no significant difference between two genotype for blood lead, age, and work duration. The proportion of ALAD1-2 genotype in control office workers was 13.2%. The proportions of ALAD1-2 genotype of lead workers were 14.0%(their mean air lead level below $0.024mg/m^3$), 10.4%($0.025-0.049mg/m^3$), 11.8%($0.050-0.099mg/m^3$), and 9.4%(above $0.100mg/m^3$), respectively. In the logistic analysis of 15 lead related symptoms, 'arthralgia'(S7) symptom of ALAD1-2 was significantly lower (OR=0.481; 95% CI=0.248-0.932) than that of ALAD1-1, but 'feeling of irritation'(S11) of ALAD1-2 was significantly higher(OR=1.636; 95% CI=1.035-2.586) than that of ALAD1-1 after controlling possible confounder (blood lead, work duration, smoking and drinking habit).

• 한국균학회소식:학술대회논문집
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• 한국균학회 2015년도 춘계학술대회 및 임시총회
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• pp.15-15
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• 2015

Aspergillus fumigatus is a major cause of invasive aspergillosis (IA), a significant health issue worldwide with high mortality rates up to 95%. Our lab is interested in how A. fumigatus adapts to low oxygen conditions 'hypoxia', which is one of the important host microenvironments. A. fumigatus SrbA is a basic helix-loop-helix (bHLH) transcriptional regulator and belongs to sterol regulatory element binding protein (SREBP) family members. Loss of SrbA completely blocks growth in hypoxia and results in avirulence in murine models of IA suggesting an essential role of SrbA in hypoxia adaptation and virulence in A. fumigatus. We conducted chromatin immunoprecipitation sequencing (ChIP-seq) with A. fumigatus wild type using a SrbA specific antibody, and 97 genes were revealed as SrbA direct targets. One of the 'SrbA regulons' (AFUB_099590) was a putative bHLH transcriptional regulator whose sequence contained a characteristic tyrosine substitution in the basic portion of the bHLH domain of SREBPs. Therefore, we designated AFUB_099590 SrbB. Further characterization of SrbB demonstrated that SrbB is important for radial growth, biomass production, and biosynthesis of heme intermediates in hypoxia and virulence in A. fumigatus. A series of quantitative real time PCR showed that transcription of several SrbA regulons is coordinately regulated by two SREBPs, SrbA and SrbB in hypoxia. This suggests that SrbA and SrbB have both dependent and independent functions in regulation of genes responsible for hypoxia adaptation in A. fumigatus. Together, our data provide new insights into complicated roles of SREBPs in adaptation of host environments and virulence in pathogenic fungi.

• 생명과학회지
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• 제28권2호
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• pp.216-222
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• 2018

Desmodium heterocarpon은 콩과에 속하는 덩굴식물로 주로 한국, 일본 등의 아시아 국가에 분포되어 있다. 본 연구에서는 식물에 존재하는 신규 기능성 소재 개발의 일환으로 Desmodium heterocarpon 에탄올 추출물(DHEE)의 항산화 및 항염증 생리활성을 DPPH 라디칼 소거능, ROS 소거능, NO 생성 억제능 및 관련 단백질 발현을 통해 분석하였다. 먼저 DHEE의 항산화능을 DPPH 라디칼 소거능을 통해 분석한 결과 높은 소거활성을 보여 DHEE가 매우 강한 항산화능을 보유함을 확인하였다. 또한 RAW 264.7 세포주에서 H2O2에 의해 유도된 ROS에 대한 DHEE의 소거능을 분석한 결과 농도의존적인 강한 ROS 소거능을 보였다. 뿐만 아니라 대표적인 항산화 효소 중 하나로 항산화능 보유 천연물에 의해 발현이 유도되는 HO-1 및 그 전사 인자인 Nrf2의 단백질 발현이 DHEE의 처리에 의해 유의적으로 증가됨을 보였다. 한편 DHEE가 LPS에 의해 유도된 NO 생성에 미치는 영향을 분석한 결과 농도 의존적인 NO 생성 저해능을 보였으며 이는 NO 생성 단백질인 iNOS의 발현 저해에서 기인함을 확인하였다. 이러한 결과를 통해 DHEE의 높은 항산화능과 항염증 활성을 확인하였으며 향후 잠재적인 기능성 소재로서 유용하게 활용될 수 있을 것으로 판단된다. 추후 계속적인 연구를 통해 활성 물질의 규명이 필요할 것으로 보인다.

• The Korean Journal of Ecology
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• 제25권5호
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• pp.335-339
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• 2002

전국 6개 지역에서 서식하는 비둘기(Columba livia) 60마리를 채집하여 간, 신장, 뼈, 허파 조직의 Fe. Zn, Mn, Cd, Pb 농도를 측정하고 조직간, 원소간 상관관계를 분석하였다. 조사 결과 조직간, 원소간에 다양한 상관관계가 있는 것으로 밝혀졌다. 조직별 원소간 상관관계에서는 독성 원소인 카드뮴의 경우 체내 축적은 장점막내의 흡수 수용체로부터의 철 흡수를 저하시키며, hemoglobin과 hematocrit의 낮은 수치를 유도하므로 두 원소간 음의 상관관계가 있는 것으로 나타났다. 간 및 신장 조직 중 독성 원소인 카드뮴과 필수 원소인 아연과는 정의 상관관계가 나타났으며, 이는 체내 항상성 유지를 위한 독성방어 메커니즘과 밀접한 관련이 있음을 시사한다. 간 조직 중 납과 철과의 정의 상관관계는 6개 지역 중 상대적으로 농도가 높은 부산지역에서만 나타났으며, 이는 납이 hemoglobin 합성을 방해하여 간 조직 내 철의 보유량을 증가시킨다는 사실을 암시한다. 원소간 조직별 상관관계에서는 오염원소인 납과 카드뮴에서 상대적으로 다른 원소에 비해 다양한 상관관계가 나타난 것으로 조사되었으며, 이러한 조직간, 원소간 상관관계는 조류를 이용한 특정지역의 오염 및 위해 정도를 모니터링하는 데 필히 고려되어야 한다는 사실을 시사한다.

• 동의생리병리학회지
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• 제22권6호
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• pp.1431-1438
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• 2008

The marine algae, Padina arborescens, have been used traditionally for treatment of various brain diseases. However, the molecular studies on the effect of Padina arborescens have not been carried out. In the present study, the protective effect of the water extract of Padina arborescens (PAWE) was researched in $H_2O_2$-treated human vascular endothelial cells, ECV304. ECV304 cells were pre-incubated with PAWE (0, 400, 800, 1,200 and $1,600{\mu}g/m{\ell}$) for 12 h and treated with 500 uM $H_2O_2$ for 12 h, and then the protective effects of PAWE were determined. PAWE recovered the $H_2O_2$-induced cell damage and decreased ROS production in ECV304 cells. Moreover, PAWE increased ERK expression and inhibited p38 and JNK expression. Furthermore, PAWE dosedependently increased the expression of heme oxygenase-1 (HO-1) and the HO-1 expression was reduced by ERK inhibitor treatment in $H_2O_2$-treated EVC304 cells. These results suggested that protective effect of PAWE on $H_2O_2$-induced oxidative stress in ECV304 cells might be associated with the production of HO-1 through the ERK signal pathway.

• Asian-Australasian Journal of Animal Sciences
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• 제23권1호
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• pp.116-121
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• 2010

Long-chain polyunsaturated fatty acids (LC-PUFA) promote the development of brain and vision of the fetus, relieve inflammation, inhibit oral dysplasia of rumor cell, decrease the incidence of cardiovascular disease and regulate arrhythmia. ${\Delta}-6$ desaturase is the rate-limited enzyme in the desaturation process. This study reports the cloning, characterization and tissue expression of a ${\Delta}-6$ desaturase gene in the chicken. PCR primers were designed based on the predicted sequence of chicken ${\Delta}-6$ desaturase (accession number: XM421053) and used to isolate a cDNA fragment of 1,323 bp from chicken liver. Based on the 1,323 bp fragment an EST (BI390105) was obtained by BLAST. The EST and 5'nd of the 1,323 bp fragment were partially overlapped. Gene specific primers derived from the EST were used for amplification of the 5'nd. Another gene-specific primer derived from the 1,323 bp fragment was used for amplification of the 3'nd by 3'ACE. Then the three overlapping cDNA sequences obtained were assembled with DNAMAN software and a full-length ${\Delta}-6$ desaturase of 2,153 bp was obtained. The full-length cDNA contained an ORF of 1,335 bp with a 5'ntranslated region of 147 nucleotides followed by an ATG initiation codon. Stop codon TGA was at position 1,481-1,483 bp. The deduced amino acids shared an homology above 77% with bovine, mice, orangutan, rat and human. The protein sequence had three histidine-rich regions HDFGH (HisI region), HFQHH (HisII region) and HH (HisIII region), a cytochrome $b_{5}$-like domain containing a heme-binding motif and two transmembrane domains. Sequence analysis of the chicken genomic DNA revealed that the coding sequence of chicken ${\Delta}-6$ desaturase included 12 exons and 11 introns. Semi-quantitative RT-PCR showed that the ${\Delta}-6$ desaturase expression levels were in turn liver, spleen, pancreas, lung, breast muscle, heart, and abdominal fat. The expression of ${\Delta}-6$ desaturase in liver was significantly higher than that in breast muscle (p<0.01). The expression of ${\Delta}-6$ desaturase in lung was significantly higher than that in abdominal fat (p<0.01). This is the first clone of chicken ${\Delta}-6$ desaturase.

• 한국식품과학회지
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• 제49권2호
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• pp.203-208
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• 2017

고지방식사를 섭취한 쥐의 신장에서 가압볶음 무말랭이 추출물의 산화방지, 항염증 효과를 확인하였다. 실험군은 chow diet와 증류수를 경구 투여하는 NOR group, 고지방식사와 증류수를 경구 투여하는 CON group, 고지방식사와 237 mg/kg bw/day농도의 DR과 RDR를 각각 경구 투여하는 DR group, RDR group으로 나누어 12주간 사육하였다. 신장의 산화스트레스 지표인 ROS, $ONOO^-$, 그리고 지방질과산화물의 농도를 확인한 결과 CON group이 NOR group에 비해 유의적으로 증가하였다. 반면 DR group과 RDR group에서 유의적으로 감소하였다. 체내 산화방지 지표인 글루타싸이온의 농도와 산화방지단백질의 발현은 DR group과 RDR group 모두 CON group에 비해 증가하였다. NF-${\kappa}B$ 발현은 CON group이 NOR group에 비해 증가하였으나 DR group과 RDR group은 모두 감소하였다. RDR group은 DR group에 비해 $ONOO^-$ 및 지방질과산화물 농도가 감소하였고 글루타싸이온 농도와 산화방지 관련 단백질 발현 중 Nrf2, HO-1, 카탈레이스, 그리고 GPx가 증가하였고 염증반응 전사인자인 NF-${\kappa}B$의 발현이 낮아졌다. RDR group의 산화스트레스 개선효과는 유의적으로 높은 것으로 확인되었다. 따라서 가압볶음무말랭이를 차로 제조하여 섭취할 때 고지방식사로 유도된 신장의 산화스트레스를 억제할 수 있을 것으로 사료되며, 그 효과는 무말랭이보다 높은 것으로 확인되었다.

• BMB Reports
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• 제39권1호
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• pp.68-75
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• 2006

In higher plants, P450s participate in the biosynthesis of many important secondary metabolites. Here we reported for the first time the isolation of a new cytochrome P450 cDNA that expressed in a stem-specific manner from Camptotheca acuminata (designated as CaSS), a native medicinal plant species in China, using RACE-PCR. The full-length cDNA of CaSS was 1735 bp long containing a 1530 bp open reading frame (ORF) encoding a polypeptide of 509 amino acids. Bioinformatic analysis revealed that CASS contained a heme-binding domain PFGXGRRXCX and showed homology to other plant cytochrome P450 monooxygenases and hydroxylases. Southern blotting analysis revealed that there was only one copy of the CaSS present in the genome of Camptotheca acuminata. Northern blotting analysis revealed that CaSS expressed, in a tissue-specific manner, highly in stem and lowly in root, leaf and flower. Our study suggests that CaSS is likely to be involved in the phenylpropanoid pathway.

• Biomolecules & Therapeutics
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• 제28권3호
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• pp.259-266
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• 2020

The present research work primarily investigated whether spinosin has the potential of improving the pathogenesis of Alzheimer's disease (AD) driven by β-amyloid (Aβ) overproduction through impacting the procession of amyloid precursor protein (APP). Wild type mouse Neuro-2a cells (N2a/WT) and N2a stably expressing human APP695 (N2a/APP695) cells were treated with spinosin for 24 h. The levels of APP protein and secreted enzymes closely related to APP procession were examined by western blot analysis. Oxidative stress related proteins, such as nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were detected by immunofluorescence assay and western blot analysis, respectively. The intracellular reactive oxygen species (ROS) level was analyzed by flow cytometry, the levels of Aβ_1-42 were determined by ELISA kit, and Thioflavin T (ThT) assay was used to detect the effect of spinosin on Aβ_1-42 aggregation. The results showed that ROS induced the expression of ADAM10 and reduced the expression of BACE1, while spinosin inhibited ROS production by activating Nrf2 and up-regulating the expression of HO-1. Additionally, spinosin reduced Aβ_1-42 production by impacting the procession of APP. In addition, spinosin inhibited the aggregation of Aβ_1-42. In conclusion, spinosin reduced Aβ_1-42 production by activating the Nrf2/HO-1 pathway in N2a/WT and N2a/APP695 cells. Therefore, spinosin is expected to be a promising treatment of AD.

• 동의생리병리학회지
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• 제28권3호
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• pp.303-309
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• 2014

The fruit of Gleditsia sinensis has been extensively used as a key ingredient of an herbal remedy for the treatment of various inflammatory diseases in traditional Korean Medicine. However, the reason of using the fruit of G. sinensis for the remedy is unclear. Since Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key anti-inflammatory transcription factor, which is activated by the fruit of G. sinesis, we examined whether other plant parts of G. sinensis are also capable of suppressing inflammatory responses by activating Nrf2. Water extracts of various parts of G. sinensis were prepared and tested for Nrf2 activation by reporter assay and western blot analysis. Our results show that the hull of G. sinensis is the most potent in activating Nrf2. Sequential organic solvent extraction of the hull show that all the fractions had a higher potency in activating Nrf2 than the water extract, albeit differential degrees. The hull originated from Korea in general activated Nrf2 strongly compared to that of China. Chloroform fraction of the hull was further examined, showing that the fraction induced nuclear localization of Nrf2, indicative of activated Nrf2, and Nrf2-dependent gene expression including NAD(P)H dehydrogenase quinone 1 (NQO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and heme oxygenase - 1 (HO-1). Therefore, our results show that, among other plant parts examined in this study, the hull of G. sinensis is the most potent, providing the experimental basis for the use of the hull of G. sinensis as an active ingredient for an anti-inflammatory remedy.