• 제목/요약/키워드: Metabolic pathway

검색결과 504건 처리시간 0.025초

Cytochrome P-450 의존성 radical 전달에 의한 Benzene, Toluene, Xylene의 대사기전 연구 (A Study on the metabolism mechanism of Benzene, Toluene and Xylene by Cytochrome P-450 dependent radical-mediated)

  • 김기웅;장성근;김양호;문영한
    • Toxicological Research
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    • 제11권2호
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    • pp.205-213
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    • 1995
  • This study was undertaken to investigate the effects of organic solvents on xenobiotic metabollzing enzyme system in vivo by meaas of experimental conditions i.e. (1) single group which was treated by benzene (B), toluene (T) and xylene (X), respectively, (2) combination group which was treated by mixture of benzene+toluene (BT), benzene+xylene (BX), and toluene+xylene (TX), respectively, (3) mixture group which was treated by benzene+ toluene+xylene mixture (M), and to interpreat the interaction between the organic solvents metabolizing enzymes. 1. The contents of cytochrome P-450 in liver microsomes were increased (p < 0.01) in organic solvents treated groups, and the contents of cytochrome P-450 were increased by following order of B < T < M < BT=BX < X < TX. 2. The activity of cytochrome P-450 dependent AHHase was significantly higher in organic solvents treated groups than in control group (p < 0.01), and the activity of AHHase was increased by following order of B < T < BT=BX=TX=xylene < M. 3. The activity of NADPH P-450 reductase was significantly higher in organic solvents treated groups than in control group (p < 0.01), and the order of M < combinated group < X < T

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Effect of Ketoconazole, a Cytochrome P450 Inhibitor, on the Efficacy of Quinine and Halofantrine against Schistosoma mansoni in Mice

  • Seif el-Din, Sayed Hassan;Abdel-Aal Sabra, Abdel-Nasser;Hammam, Olfat Ali;El-Lakkany, Naglaa Mohamed
    • Parasites, Hosts and Diseases
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    • 제51권2호
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    • pp.165-175
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    • 2013
  • The fear that schistosomes will become resistant to praziquantel (PZQ) motivates the search for alternatives to treat schistosomiasis. The antimalarials quinine (QN) and halofantrine (HF) possess moderate antischistosomal properties. The major metabolic pathway of QN and HF is through cytochrome P450 (CYP) 3A4. Accordingly, this study investigates the effects of CYP3A4 inhibitor, ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver. QN and HF significantly (P<0.05) elevated malondialdehyde levels when used alone or with KTZ. Meanwhile, KTZ plus QN or HF restored serum levels of ALT, albumin, and reduced hepatic glutathione (KTZ+HF) to their control values. KTZ enhanced the therapeutic antischistosomal potential of QN and HF over each drug alone. Moreover, the effect of KTZ+QN was more evident than KTZ+HF.

황 함유 필수아미노산이 증대된 기능성 형질전환 감자 개발 현황 (Development of transgenic potato with high content of sulphur-containing essential amino acids)

  • 구영민;김태원;이민경;이신우
    • Journal of Plant Biotechnology
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    • 제40권1호
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    • pp.1-8
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    • 2013
  • 감자는 벼, 보리, 밀과 함께 세계 4 대 식량작물에 속하며 고품질의 전분과 함께 비타민 C 함량이 높고 단백질의 함량도 높다. 그러나 메티오닌과 시스테인 등의 황 함유 아미노산과 함께 필수아미노산이 부족하여 영양학적으로 가치가 다소 낮다는 것이 단점이다. 따라서 최근에는 유전자재조합 기술 및 대사공학기술을 이용하여 이들 필수아미노산의 함량을 증대시키기 위한 연구가 활발히 진행되고 있다. 본 논문에서는 황 함유 필수 아미노산의 함량을 증가시키기 위한 연구현황 및 문제점 등을 조사하였다.

Transcriptome analysis of a medicinal plant, Pistacia chinensis

  • Choi, Ki-Young;Park, Duck Hwan;Seong, Eun-Soo;Lee, Sang Woo;Hang, Jin;Yi, Li Wan;Kim, Jong-Hwa;Na, Jong-Kuk
    • Journal of Plant Biotechnology
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    • 제46권4호
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    • pp.274-281
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    • 2019
  • Pistacia chinensis Bunge has not only been used as a medicinal plant to treat various illnesses but its young shoots and leaves have also been used as vegetables. In addition, P. chinensis is used as a rootstock for Pistacia vera (pistachio). Here, the transcriptome of P. chinensis was sequenced to enrich genetic resources and identify secondary metabolite biosynthetic pathways using Illumina RNA-seq methods. De novo assembly resulted in 18,524 unigenes with an average length of 873 bp from 19 million RNA-seq reads. A Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation tool assigned KO (KEGG orthology) numbers to 6,553 (36.2%) unigenes, among which 4,061 unigenes were mapped into 391 different metabolic pathways. For terpenoid backbone and carotenoid biosynthesis pathways, 44 and 22 unigenes encode enzymes corresponding to 30 and 16 entries, respectively. Twenty-two unigenes encode proteins for 16 entries of the carotenoid biosynthesis pathway. As for the phenylpropanoid and flavonoid biosynthesis pathways, 63 and 24 unigenes were homologous to 17 and 14 entry proteins, respectively. Mining of simple sequence repeat identified 2,599 simple sequence repeats from P. chinensis unigenes. The results of the present study provide a valuable resource for in-depth studies on comparative and functional genomics to unravel the underlying mechanisms of the medicinal properties of Pistacia L.

Curcumin Conjugates Induce Apoptosis Via a Mitochondrion Dependent Pathway in MCF-7 and MDA-MB-231 Cell Lines

  • Singh, Durg Vijay;Agarwal, Shikha;Singh, Preeti;Godbole, Madan Madhav;Misra, Krishna
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권10호
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    • pp.5797-5804
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    • 2013
  • In order to enhance the bioavailability of curcumin its conjugates with piperic acid and glycine were synthesized by esterifying the 4 and 4' phenolic hydroxyls, the sites of metabolic conjugation. Antiproliferative and apoptotic efficacy of synthesized conjugates was investigated in MCF-7 and MDA-MB-231 cell lines. $IC_{50}$ values of di-O-glycinoyl (CDG) and di-O-piperoyl (CDP) esters of curcumin were found to be comparable with that of curcumin. Both conjugates induced chromatin condensation fragmentation and apoptotic body formation. CDP exposure to MCF-7 cells induced apoptosis initiating loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) followed by inhibition of translocation of transcription factor NF-${\kappa}B$ and release of Cytochrome-C. Reactive oxygen species (ROS) production was evaluated by fluorescent activated cell sorter. Change in ratio of Bcl2/Bclxl was observed, suggesting permeablization of mitochondrial membrane leading to the release of AIF, Smac and other apoptogenic molecules. DNA fragmentation as a hallmark for apoptosis was monitored by TUNEL as well as agrose gel electrophoresis. Thus, it was proven that conjugation does not affect the therapeutic potential of parent molecule in vitro, while these could work in vivo as prodrugs with enhanced pharmacokinetic profile. Pharmacokinetics of these molecules under in vivo conditions is a further scope of this study.

Molecular Characterization and Expression of LDHA and LDHB mRNA in Testes of Japanese Quail (Coturnix japonica)

  • Singh, R.P.;Sastry, K.V.H.;Pandey, N.K.;Shit, N.G.;Agarwal, R.;Singh, R.;Sharma, S.K.;Saxena, V.K.;Jagmohan, Jagmohan
    • Asian-Australasian Journal of Animal Sciences
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    • 제24권8호
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    • pp.1060-1068
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    • 2011
  • The LDH isozymes are key catalysts in the glycolytic pathway of energy metabolism. It is well known that the distribution of the LDH isozymes vary in accordance with the metabolic requirements of different tissues. The substrates required for energy production change noticeably at successive stages of testes development suggesting a significant flexibility in the expression of glycolytic enzymes. Therefore, expression of LHDA and LDHB mRNAs was examined in adult and prepubertal quail testis. The mRNA of both LDHA and LDHB were expressed and no significant difference was observed in prepubertal testes. The mRNA levels of LDHB significantly increased during testicular development. In the adult testis, LDHA mRNA was not expressed. Expression studies revealed the presence of different LDH isozymes during testicular development. In contrast, electrophoresis of both testicular samples revealed only single band at a position indicative of an extreme type of LDH isozyme in quail testes. Furthermore, nucleotide and amino acid sequence analysis revealed significant similarity to chicken, duck and rock pigeon. These sequence results confirmed the similarity of LDHA and LDHB subunit protein in different avian species.

식이제한이 흰쥐의 체내대사에 미치는 영향 (The Effect of 50% dietary restriction on Protein and Nucleic acid Metabolism of Albino rats)

  • 최길자;김숙희
    • Journal of Nutrition and Health
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    • 제3권3호
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    • pp.167-178
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    • 1970
  • 체중이 $43{\pm}2g$ 되는 흰쥐 암수 70마리를 7 group으로 나누어 Sugar-casein diet를 사료로 하여 pair-feeding에 의한 50% 식이제한으로 9주간 사육한 실험결과는 다음과 같다. 50%식이제한으로 나타나는 현상은 체중감소와 더불어 각 장기의 무게가 감소하였고 실험기간이 길어질수록 감소율이 높았다. 각 장기중 간과 비장의 무게의 감소가 심했고 뇌가 가장 영향을 적게 받았다. 질소의 체내 보유율은 식이제한 group이 control group 보다 높았으나 몸무게 g당 체내 보유율은 식이제한 group이 높았고 식이제한 group의 몸무게는 감소하여 신체 내에서 단백질의 경제적연 이용을 알 수 있다. 식이제한으로 인한 각장기의 질소 RNA, DNA함량은 비장이 식이제한에 가장 예민하고 뇌가 가장 둔한 경향을 나타내었다. 식이제한으로 Hematology에 뚜렷한 변화는 없고 식이제한으로 anemia의 현상이 나타난다고는 할 수 없고 Serum albumin 이나 A/G Ratio도 두 group 사이에 식이제한 전기간을 통해 차이가 없었다.

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Effect of BIS depletion on HSF1-dependent transcriptional activation in A549 non-small cell lung cancer cells

  • Yun, Hye Hyeon;Baek, Ji-Ye;Seo, Gwanwoo;Kim, Yong Sam;Ko, Jeong-Heon;Lee, Jeong-Hwa
    • The Korean Journal of Physiology and Pharmacology
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    • 제22권4호
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    • pp.457-465
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    • 2018
  • The expression of BCL-2 interacting cell death suppressor (BIS), an anti-stress or anti-apoptotic protein, has been shown to be regulated at the transcriptional level by heat shock factor 1 (HSF1) upon various stresses. Recently, HSF1 was also shown to bind to BIS, but the significance of these protein-protein interactions on HSF1 activity has not been fully defined. In the present study, we observed that complete depletion of BIS using a CRISPR/Cas9 system in A549 non-small cell lung cancer did not affect the induction of heat shock protein (HSP) 70 and HSP27 mRNAs under various stress conditions such as heat shock, proteotoxic stress, and oxidative stress. The lack of a functional association of BIS with HSF1 activity was also demonstrated by transient downregulation of BIS by siRNA in A549 and U87 glioblastoma cells. Endogenous BIS mRNA levels were significantly suppressed in BIS knockout (KO) A549 cells compared to BIS wild type (WT) A549 cells at the constitutive and inducible levels. The promoter activities of BIS and HSP70 as well as the degradation rate of BIS mRNA were not influenced by depletion of BIS. In addition, the expression levels of the mutant BIS construct, in which 14 bp were deleted as in BIS-KO A549 cells, were not different from those of the WT BIS construct, indicating that mRNA stability was not the mechanism for autoregulation of BIS. Our results suggested that BIS was not required for HSF1 activity, but was required for its own expression, which involved an HSF1-independent pathway.

De novo gene set assembly of the transcriptome of diploid, oilseed-crop species Perilla citriodora

  • Kim, Ji-Eun;Choe, Junkyoung;Lee, Woo Kyung;Kim, Sangmi;Lee, Myoung Hee;Kim, Tae-Ho;Jo, Sung-Hwan;Lee, Jeong Hee
    • Journal of Plant Biotechnology
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    • 제43권3호
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    • pp.293-301
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    • 2016
  • High-quality gene sets are necessary for functional research of genes. Although Perilla is a commonly cultivated oil crop and vegetable crop in Southeast Asia, the quality of its available gene set is insufficient. To construct a high-quality Perilla gene set, we sequenced mRNAs extracted from different tissues of Perilla citriodora, the wild species (2n = 20) of Perilla. To make a high-quality gene set for P. citriodora, we compared the quality of assemblies produced by Velvet and Trinity, the two well-known de novo assemblers, and improved the de novo assembly pipeline by optimizing k-mers and removing redundant sequences. We then selected representative transcripts for loci according to several criteria. The improved assembly yielded a total of 86,396 transcripts and 38,413 representative transcripts. We evaluated the assembled transcripts by comparing them to 638 homologous Arabidopsis genes involved in fatty acid and TAG biosynthesis pathways. High proportions of full-length genes and transcripts in the assembled transcripts matched known genes in other species, indicating that the P. citriodora gene set can be applied in future functional studies. Our study provides a reference P. citriodora gene set for further studies. It will serve as valuable genetic resource to elucidate the molecular basis of various metabolisms.

Genotoxicity and Identification of Differentially Expressed Genes of Formaldehyde in human Jurkat Cells

  • Kim, Youn-Jung;Kim, Mi-Soon;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • 제1권4호
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    • pp.230-236
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    • 2005
  • Formaldehyde is a common environmental contaminant found in tobacco smoke, paint, garments, diesel and exhaust, and medical and industrial products. Formaldehyde has been considered to be potentially carcinogenic, making it a subject of major environmental concern. However, only a little information on the mechanism of immunological sensitization and asthma by this compound has been known. So, we performed with Jurkat cell line, a human T lymphocyte, to assess the induction of DNA damage and to identify the DEGs related to immune response or toxicity by formaldehyde. In this study, we investigated the induction of DNA single strand breaks by formaldehyde using single cell gel electrophoresis assay (comet assay). And we compared gene expression between control and formaldehyde treatment to identify genes that are specifically or predominantly expressed by employing annealing control primer (ACP)-based $GeneFishing^{TM}$ method. The cytotoxicity ($IC_{30}$) of formaldehyde was determined above the 0.65 mM in Jurkat cell in 48 h treatment. Based on the $IC_{30}$ value from cytotoxicity test, we performed the comet assay in this concentration. From these results, 0.65 mM of formaldehyde was not revealed significant DNA damages in the absence of S-9 metabolic activation system. And the one differentially expressed gene (DEG) of formaldehyde was identified to zinc finger protein 292 using $GeneFishing^{TM}$ method. Through further investigation, we will identify more meaningful and useful DEGs on formaldehyde, and then can get the information on the associated mechanism and pathway with immune response or other toxicity by formaldehyde exposure.