• 제목/요약/키워드: Cytochrome P450

검색결과 936건 처리시간 0.027초

굴, 김 및 조피볼락에서 다환성방향족탄화수소(Polycyclic Aromatic Hydrocarbons, PAHs)의 잔류에 미치는 요인에 대한 연구 (Factors Affecting Concentration of Polycyclic Aromatic Hydrocarbons in Oyster, Laver and Rockfish)

  • 김강전;최상훈;박관하
    • 한국패류학회지
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    • 제24권3호
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    • pp.253-260
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    • 2008
  • 각각 20 시료씩 최대한 다양한 산지에서 생산된 것으로 추정되는 참굴, 김 및 조피볼락을 시중에서 수집하여 이들 수산 식품에 존재하는 15 종의 다환성 방향족 탄화수소류 (polycyclic aromatic hydrocarbons, PAHs)의 잔류량을 분석하였다. 그 결과 1종의 PAHs라도 발견되는 시료의 비율은 참굴 전육질부(75%), 조피볼락 간췌장(35%), 조피볼락 근육(0%), 건조 김(0%) 순이었다. 이런 차이가 나타나도록 영향을 미치는 요인을 분석하기 위해 실험실에서 대표적 PAHs의 하나인 phenanthrene을 이 세 종의 생물에 0.01 및 $0.1{\mu}g/mL$의 농도로 2주간 노출시켰다. 참굴의 소화선, 김, 조피볼락의 간췌장에서 높은 축적성이 관찰되었지만 굴의 전 육질부(소화선 포함)나 조피볼락의 근육에서는 낮은 축적성이 관찰되었다. 생물 종간의 실험실 노출에서의 축적성 차이와 시중 시료에서 발견된 잔류성 차이는 관련성이 거의 없었다. PAHs는 소수성이 강한 물질이기 때문에 생물 종간 지방 함량을 분석하여 지방함량이 PAHs 축적성에 관련되는 지를 평가하였다. 조피볼락의 간췌장이 근육에 비해 지질 함량이 높았고 phenanthrene 축적성도 높은 것으로 조사되어 조피볼락에서 지질 함량이 간췌장으로의 PAHs의 축적에 어느 정도 기여하는 것으로 추정되었지만 다른 생물에서는 지질 함량에 따른 phenanthrene 축적성 차이가 없었다. 또한 PAHs 대사를 통한 배설 정도를 평가하기 위해 cytochrome $P_{450}$ 효소의 하나인 7-ethyoxyresorufin-O-deethylase(EROD)의 활성을 분석한 결과, 조피볼락에서는 참굴 보다 EROD 활성이 훨씬 높게 나타나 조피볼락에서 참굴보다 PAHs의 제거가 더 활발하였음을 추정할 수 있었고 그 결과로 인해 조피볼락에서 상대적으로 PAHs 검출 빈도를 낮게 나타난 것으로 추정된다. 그러나 본 연구에서 분석되지 않은 인자들 예를 들면, 생물간 노출 조건의 차이, 도피 능력, 섭이를 통한 축적 및 가공 과정에서의 소실 등에 대한 평가는 더 조사해야 할 부분이다.

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갈화가 에탄올을 투여한 흰쥐의 지질과산화와 알코올 대사효소의 활성도에 미치는 영향 (Effects of Flower of Pueraria lobata on Lipid Peroxidation and Activities of Alcohol Metabolic Enzymes in Alcohol-treated Rats)

  • 이정숙;김나영;이경희;김갑순;박희준;최종원;김석화
    • 한국식품영양과학회지
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    • 제29권5호
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    • pp.935-942
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    • 2000
  • 갈화(flower of Pueraria lobata) 분획 및 활성 성분의 급여가 아급성 알코올 중독된 흰쥐에서의 해독에 미치는 영향을 연구할 목적으로, 25% alcohol을 6주간 투여하여 아급성 알코올 중독상태를 유발한 흰쥐를 3주 더 사육하면서 혈액중 지질 함량의 변동, 알코올 대사계 효소의 활성을 비교 검퇀 결과는 다음과 같다. 알코올 단독 급여군은 대조군에 비하여 체중이 감소되었으며, 알코올-갈화 tectorigenin 급여군의 체중증가량은 대조군 수준에는 미치지 못하였으나, 알코올 단독 급여군보다는 유의적인 회복을 나타냈다. 알코올 단독 급여군의 총지방, 중성 지방, 인지질 함량이 대조군에 비하여 중가하엿고, 알코올-갈화 tcctorigcnin 급여군과 알코올-갈화 kaikasapomin III 급여군의 총지방, 주성지방 함량은 대조군 수준에는 미치지 못하였으나, 알코올 단독 급여군에 비하여 유의적으로 회복되었다. 알코올 단독 급여군의 total cholesterol, LDL-cholesterol, VLDL-cholesterol 함량, AI는 대조군에 비하여 증가하였고, 알코올-갈화 tectorigcnin, kaikasaponin III 급여군은 대조군 수준에는 미치지 못했으나, 알코올 단독 급여군에 버해 유의적으로 회복되았다. 알코올 단독 급여군의 HDL-cholcsterol의 함량은 대조군에 비하여 감소하던 것이 알코올-갈화 tectorigenin 급여군과 알코올-갈화 kaikasaponin III 급여군에서는 대조군 수준에서는 미치지 못하나, 알코올 단독 급여군에 비하여 증가하였다. 알코올 급여 시 cytochrome P 450, AH와 AD활성은 대조군에 비하여 증가했으나, 알코올-갈화 tectorigenin 급여군과 알코올-갈화 kaikasaponin III 급여군의 경우 알코올 단독 급여군보다 낮게 나타났다. 알코올 급여시 ADH활성이 증가하였으며 알코올-갈화 tectorigenin 급여군과 알코올-갈화 kaikasponin III 급여군은 알코올 단독 급여군보다 높게 나타났다. MEOS의 활성은 알코올 급여 시 대조군에 비하여 중가를 보였고, 알코올-갈화 tectorigenin 급여군에서는 알코올 단독 급여군보다 유의적인 증가를 나타냈다. Catalase의 활성은 각 군간의 유의적인 차이를 볼 수 없었다. ALDH의 활성은 알코올 단독 급여군은 대조군의 활성에 비하여 감소되었으나, 알코올-갈화 tectorigenin 급여군과 알코올-갈화 kaikasaponin III 급여군에서 알코올 단독 급여군보다 유의적인 활성증가를 보였다. 이상의 결과를 종합해 볼 때 갈화로부터 분리된 tectorigenin과 kaikasaponin III는 아급성 알코올 중독된 흰쥐 간의 free radical 생성계 효소를 억제시켜 알코올로 인한 간손상을 회복시키고, 알코올 대사 효소계에 관여하여 해독작용에 영향을 미침으로써 알코올 해독에 도움을 줄 수 있을 것으로 사료된다.

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RNA sequencing을 이용한 염 스트레스 처리 밀(Triticum aestivum)의 유전자 발현 차이 확인 및 후보 유전자 선발 (Transcriptomic Analysis of Triticum aestivum under Salt Stress Reveals Change of Gene Expression)

  • 전동현;임윤호;강유나;박철수;이동훈;박준찬;최우찬;김경훈;김창수
    • 한국작물학회지
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    • 제67권1호
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    • pp.41-52
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    • 2022
  • 1. 본 연구에서는 우리밀 품종인 금강밀과 염 저항성을 가지는 돌연변이 라인 2020-s1340을 재료로 200 mM 염 스트레스 처리에 따른 전사체 발현을 확인하였다. QuantSeq을 통해 23,634,438개의 reads가 생산되었고 7,331,269개의 reads가 mapping됐다. 2. 염 스트레스 상황에서 총 282개의 DEG가 확인이 되었고 이러한 DEGs는 UDP-glucosyltransferase, receptor kinase-like protein, Lectin receptor-like kinases, cytochrome P450등의 단백질들을 코딩하는 유전자들이다. 이러한 DEGs는 염 저항성과 관련된 후보 유전자들이 될 수 있다. 염 저항성과 관련하여 역할이 밝혀지지 않은 유전자들은 추후 연구를 통해 확인이 필요하다. 3. GO연구에서는 DEGs를 세가지 범주로 분류하였으며 대부분 식물체 내 세포 기초 경로와 관련된 GO term들이 주로 되었으며 각각 범주에 있어서 biological process, molecular process에서는 single-organism process (GO: 0044699), single-organism metabolic process (GO:0044710), oxidation-reduction process (GO:0055114), copper ion transport (GO:0006825), copper ion transmembrane transport (GO:0035434), alternative oxidase activity (GO:0009916) GO term들이 유의성이 높게 나타났다. 4. 이러한 QuantSeq의 분석결과는 밀에 관한 염에 의해 발현되는 전사 발현에 대한 이해를 향상시킬 수 있다. 또한 염 스트레스 반응의 복잡한 분자 메커니즘에 대한 좋은 통찰력을 제공하고 염분 스트레스에 대한 작물 내성의 유전적 개선을 위한 실질적인 토대를 마련할 수 있을 것이다.

miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone

  • Lee, Su-Yeon;Kang, Youn-Jung;Kwon, Jinie;Nishi, Yoshihiro;Yanase, Toshihiko;Lee, Kyung-Ah;Koong, Mi Kyoung
    • Clinical and Experimental Reproductive Medicine
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    • 제47권3호
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    • pp.194-206
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    • 2020
  • Objective: The aim of this study was to investigate microRNAs (miRNAs) related to follicle-stimulating hormone (FSH) responsiveness using miRNA microarrays and to identify their target genes to determine the molecular regulatory pathways involved in FSH signaling in KGN cells. Methods: To change the cellular responsiveness to FSH, KGN cells were treated with FSH receptor (FSHR)-specific small interfering RNA (siRNA) followed by FSH. miRNA expression profiles were determined through miRNA microarray analysis. Potential target genes of selected miRNAs were predicted using bioinformatics tools, and their regulatory function was confirmed in KGN cells. Results: We found that six miRNAs (miR-1261, miR-130a-3p, miR-329-3p, miR-185-5p, miR-144-5p and miR-4463) were differentially expressed after FSHR siRNA treatment in KGN cells. Through a bioinformatics analysis, we showed that these miRNAs were predicted to regulate a large number of genes, which we narrowed down to cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and estrogen receptor alpha (ESR1) as the main targets for miR-4463. Functional analysis revealed that miR-4463 is a regulatory factor for aromatase expression and function in KGN cells. Conclusion: In this study, we identified differentially expressed miRNAs related to FSH responsiveness. In particular, upregulation of miR-4463 expression by FSHR deficiency in human granulosa cells impaired 17β-estradiol synthesis by targeting CYP19A1 and ESR1. Therefore, our data might provide novel candidates for molecular biomarkers for use in research into poor responders.

Susceptibility of Lung Cancer with Polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 Genotypes in the Population of Inner Mongolia Region

  • Jiang, Xue-Yan;Chang, Fu-Hou;Bai, Tu-Ya;Lv, Xiao-Li;Wang, Min-Jie;Wang, Guang
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권13호
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    • pp.5207-5214
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    • 2014
  • Background: To study the relationship of susceptibility to lung cancer with the gene polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1, GSTP1 and smoking status in Han and Mongolian populations of Inner Mongolia, an autonomous region of China. Materials and Methods: PCR-RFLP, allele-specific and multiplex PCR were employed to identify the genotypes of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 in a case-control study of 322 lung cancer patients diagnosed by bronchoscopy and 456 controls free of malignancy. Results: There is a significant difference in genotypic frequency of GSTT1 of healthy Mongolian and Han subjects. A statistically prominent association was found between CYP1A1 Msp1 (vt/vt) (OR=4.055, 95%CI:2.107-7.578, p=0.000), GSTM1 (-) (OR=2.290, 95%CI:1.467-3.573, p=0.000) and lung cancer in Mongolians. Similarly, in the Han population, CYP1A1 Msp1 (vt/vt) (OR=3.194, 95%CI:1.893-5.390, p=0.000) and GSTM1 (-) (OR=1.884, 95%CI:1.284-2.762, p=0.001) carriers also had an elevated risk of lung cancer. The smokers were more susceptible to lung cancer 2.144 fold and 1.631 fold than non-smokers in Mongolian and Han populations, respectively. The smokers who carried with CYP1A1 Msp1 (wt/vt+vt/vt), exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3 (AB+BB), and GSTT1 (-) respectively were found all to have a high risk of lung cancer. Conclusions: CYP1A1 Msp1 (vt/vt) and GSTM1 (-) are risk factors of lung cancer in Han and Mongolian population in the Inner Mongolia region. The smokers with CYP1A1 Msp1 (wt/vt+vt/vt), CYP1A1 exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3 (AB+BB), and GSTT1 (-) genotypes, respectively, are at elevated risk of lung cancer.

Tumorigenic Effects of Endocrine-disrupting Chemicals are Alleviated by Licorice (Glycyrrhiza glabra) Root Extract through Suppression of AhR Expression in Mammalian Cells

  • Chu, Xiao Ting;de la Cruz, Joseph;Hwang, Seong Gu;Hong, Heeok
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권12호
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    • pp.4809-4813
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    • 2014
  • Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a representative EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells, used as a tumor model, were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. The expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, was also down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analysis also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated diseases.

Tumorigenic Effects of Endocrine-Disrupting Chemicals are Alleviated by Licorice (Glycyrrhiza glabra) Root Extract through Suppression of AhR Expression in Mammalian Cells

  • Chu, Xiao Ting;Cruz, Joseph Dela;Hwang, Seong Gu;Hong, Heeok
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권13호
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    • pp.5117-5121
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    • 2014
  • Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells were used as a tumorigenic model. These were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. Expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, were subsequently down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD and various concentrations of LRE showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analyses also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated disease.

TCDD로 유발된 Oxidative Stress에 대한 생약재 추출물의 방어 및 해독효과 (Protection and Detoxification Effects of Oriental Herb Extract Mixture on TCDD-Induced Oxidative Stress)

  • 황진국;이경진;양희진;박기문
    • 한국식품영양과학회지
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    • 제37권3호
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    • pp.294-301
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    • 2008
  • 본 연구는 삼백초(aururus chinensis), 포공영(Taraxacum platycarpum), 유근피(Ulmus macrocarpa), 감초(Glycyrrhiza glabra), 흑두(Rhynchosia nulubilis)로부터 제조된 생약재 추출 혼합물이 dioxin 중 중독성이 가장 강하다고 알려진 2,3,7,8-tetrachlorodinenzo-p-dioxin(TCDD)에 의한 산화적 스트레스에 미치는 효과를 실험하였다. 정상적인 간세포주를 TCDD에 노출시킨 후 OHEM을 처리한 결과, TCDD에 의한 세포독성을 감소시켰으며, 간세포주로부터 생성된 lactate dehydrogenase, nitric oxide, cytochrome p450의 생성량 측정 결과로 OHEM이 TCDD로 유발된 간 독성을 해독할 수 있는 것으로 나타났다. 그리고 rat을 이용한 TCDD 급성독성 유발 실험에서는 TCDD 투여에 의해 증가된 AST, ALT, ALP, LDH 및 동맥경화지수가 OHEM의 투여에 의해 유의성 있게 감소하였으며 OHEM의 사전투여에 의한 방어효과가 높은 것으로 측정되었다(p<0.05). 또한 OHEM의 투여가 TCDD에 의해 손상된 간세포 조직의 풍선 병변과 공포화를 감소시켰고, 소장 세포의 조직에서는 융모 조직의 부종을 현저하게 감소시켰다.

Construction of High Sensitive Detection System for Endocrine Disruptors with Yeast n-Alkane-assimilating Yarrowia lipolytica

  • Cho, Eun-Min;Lee, Haeng-Seog;Eom, Chi-Yong;Ohta, Akinori
    • Journal of Microbiology and Biotechnology
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    • 제20권11호
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    • pp.1563-1570
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    • 2010
  • To construct a highly sensitive detection system for endocrine disruptors (EDs), we have compared the activity of promoters with the n-alkane-inducible cytochrome P450 gene (ALK1), isocitrate lyase gene (ICL1), ribosomal protein S7 gene (RPS7), and the translation elongation factor-1${\alpha}$ gene (TEF1) for the heterologous gene in Yarrowia lipolytica. The promoters were introduced into the upstream of the lacZ or hERa reporter genes, respectively, and the activity was evaluated by ${\beta}$-galactosidase assay for lacZ and Western blot analysis for hER${\alpha}$. The expression analysis revealed that the ALK1 and ICL1 promoters were induced by n-decane and by EtOH, respectively. The constitutive promoter of RPS7 and TEF1 showed mostly a high level of expression in the presence of glucose and glycerol, respectively. In particular, the TEF1 promoter showed the highest ${\beta}$-galactosidase activity and a significant signal by Western blotting with the anti-estrogen receptor, compared with the other promoters. Moreover, the detection system was constructed with promoters linked to the upstream of the expression vector for the hER${\alpha}$ gene transformed into the Y. lipolytica with a chromosome-integrated lacZ reporter gene under the control of estrogen response elements (EREs). It was indicated that a combination of pTEF1p-hER${\alpha}$ and CXAU1-2XERE was the most effective system for the $E_2$-dependent induction of the ${\beta}$-galactosidase activity. This system showed the highest ${\beta}$-galactosidase activity at $10^{-6}\;M\;E_2$, and the activity could be detected at even the concentration of $10^{-10}\;M\;E_2$. As a result, we have constructed a strongly sensitive detection system with Y. lipolitica to evaluate recognized/suspected ED chemicals, such as natural/synthetic hormones, pesticides, and commercial chemicals. The results demonstrate the utility, sensitivity, and reproducibility of the system for identifying and characterizing environmental estrogens.

The Roles of Arachidonic Acid and Calcium in the Angiotensin II-induced Inhibition of $Na^+$ Uptake in Renal Proximal Tubule Cells

  • Park, Soo-Hyun;Koh, Hyun-Joo;Lee, Yeun-Hee;Son, Chang-Ho;Park, Min-Kyoung;Lee, Young-Jae;Han, Ho-Jae
    • The Korean Journal of Physiology and Pharmacology
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    • 제3권1호
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    • pp.83-91
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    • 1999
  • Angiotensin II (ANG II) has a biphasic effect on $Na^+$ transport in proximal tubule: low doses of ANG II increase the $Na^+$ transport, whereas high doses of ANG II inhibit it. However, the mechanisms of high dose ANG II-induced inhibition on $Na^+$ uptake are poorly understood. Thus the aim of the present study was to investigate signal transduction pathways involved in the ANG II-induced inhibition of $Na^+$ uptake in the primary cultured rabbit renal proximal tubule cells (PTCs) in hormonally defined serum-free medium. ANG II $(10^{-9}\;M)-induced$ inhibition of $Na^+$ uptake was blocked by losartan $(10^{-8}\;M,\;AT_1\;antagonist),$ but not by PD123319 $(10^{-8}\;M,\;AT_2\;antagonist)$ (P<0.05). ANG II-induced inhibition of $Na^+$ uptake was also completely abolished by neomycin $(10^{-4}\;M,$ PLC inhibitor), W-7 $(10^{-4}\;M,$ calmodulin antagonist), and $AACOCF_3\;(10^{-6}\;M,\;PLA_2\;inhibitor)$ (P<0.05). ANG II significantly increased $[^3H]arachidonic$ acid (AA) release compared to control. The ANG II-induced $[^3H]AA$ release was blocked by losartan, $AACOCF_3,$ neomycin, and W-7, but not by PD123319. ANG II-induced $[^3H]AA$ release in the presence of extracellular $Ca^{2+}$ was greater than in $Ca^{2+}-free$ medium, and it was partially blocked by TMB-8 $(10^{-4}\;M,$ intracelluar $Ca^{2+}$ mobilization blocker). However, in the absence of extracellular $Ca^{2+},$ it was completely blocked by TMB-8. In addition, econazole $(10^{-6}\;M,$ cytochrome P-450 monooxygenase inhibitor) and indomethacin $(10^{-6}\;M,$ cyclooxygenase inhibitor) blocked ANG II-induced inhibition of $Na^+$ uptake, but NGDA $(10^{-6}\;M,$ lipoxygenase inhibitor) did not affect it. In conclusion, $PLA_2-mediated$ AA release is involved in ANG II-induced inhibition of $Na^+$ uptake and is modulated by $[Ca^{2+}]_i$ in the PTCs.

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