• Title/Summary/Keyword: Trans-human

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돼지 간장으로 부터 정제한 천연 단백성 Methylation Inhibitor의 S-Farnesylcysteine Methyltransferase 억제효과

  • 남석우;유세근;서동완;남태균;이향우;홍성열
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.262-262
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    • 1994
  • Ras oncogene의 산물로서 대부분의 암조직이나 transformed human cell에서 거의 공통적으로 발견되는 p21 단백질은 C-terminal processing에 의해 먼저 C-terminal cysyeine에 palmition 된 후 carboxylmethylation 된다. Palmitation은 transforming activity의 요건인 세포막에 대한 친화력을 유지시키기 위한것으로 추측되며, cysteine residue의 carboxylmethylation의 의미는 아직 확실히 밝혀지고 있지 않으나 세포막에 대한 친화력을 증가 시키는 것으로 추측되고있다. 본 연구에서는 S-Farnesylcysteine Methyltransferase의 기질로서 N-acetyl-S-trans, trans-farnesyl-L-cysteine(AFC)을 합성하였으며, 본 실험실에서 계속 연구하여 온 돼지 간장으로 부터 정제한 천연 단백성 Methylation Inhibitor의 S-Farnesylcysteine Methyltransferase 활성에 대한 억제효과를 검색하였다. 천연 단백성 Methylation Inhibitor는 돼지 간조직의 soluble fraction을 열처리하여 Sephadex G-25 column chromatngraphy한 후 reverse phase HPLC로 정제하였다. 본 inhibitor는 약 10개의 아미노산으로 구성된 peptide성 천연물질로 분자량은 1,400 Da 으로서 합성한 AFC를 기질로 하였을 때, 흰쥐 뇌 조직내 S-Farnesylcysteine methyltransferase에 대한 $IC_{50}$/은 0,82 $\times$ $10^{-6}$ M이었으며 또한 human cancer cell line의 S-Farnesylcysteine Methyltransferase에 대해서도 현저한 저해효과를 나타내었다.

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cis-Annonacin and (2,4)-cis-and trans-Isoannonacins: Cytotoxic Monotetrahydrofuran Annonaceous Acetogenins from the Seeds of Annona cherimolia

  • Woo, Mi-Hee;Chung, Soon-Ok;Kim, Dal-Hwan
    • Archives of Pharmacal Research
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    • v.22 no.5
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    • pp.524-528
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    • 1999
  • cis-Annonacin (1) and the mixture of (2,4)-cis-and trans-isoannonacins (2 and 3), three known mono-tetrahydrofuran annonaceous acetogenins, have been isolated form the seeds of Annona cherimolia by the use of the brine shrimp lethality test (BST) for bioactivity directed fractionation. Their structures were elucidated based on spectroscopic and chemical methods. 1 showed potent cytotoxicities in the brine shrimp lethality test (BST) and among six human solid tumor cell lines with notable selectivity for the pancreatic cell line (PaCa-2) at about 1,000 times the potency of adriamycin. The mixture of 2 and 3 is over 10,000 times cytotoxic as adriamycin in the pancreatic cell line (PaCa-2). All of the compounds are about 10 to 100 times as cytotoxic as adriamycin in the prostate cell line (PC-3).

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effects of the Iron Silk Road construction on Northeast sia's economy (국제철도(철의실크로드)운송이 동북아 경제역교에 미치는 영향과 효과에 관한 연구)

  • Park Heong-Soon
    • Proceedings of the KSR Conference
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    • 2005.11a
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    • pp.494-499
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    • 2005
  • Transportation routes by land like a human being blood vessel should exist for economic and trade exchange in Northeast Asia. Thinking from this point of view. I believe that TSR(Trans Siberian Railroad) and TCR(Trans Chinese Railroad). which will be connected with I would like to talk about .not only the effects of various international railroads and their connections but also economic activation TKR(Trans Korean Railroad). can play important roles. In this study, and effects in Northeast Asia which will be resulted from various international railroads construction. I tried to figure out comparative superiority and comparative advantage of the trade structure and industries in South and North Korea to find out the possibility of economic unification in East Asia. especial1y in Northeast Asia. This study also includes the effort to find out how trade exchange between South and North Korea can be expanded as a result of being a member of East Asia economic zone.

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Role of TGF-β1/SMADs signalling pathway in resveratrol-induced reduction of extracellular matrix deposition by dexamethasone-treated human trabecular meshwork cells

  • Amy Suzana Abu Bakar;Norhafiza Razali;Renu Agarwal;Igor Iezhitsa;Maxim A. Perfilev;Pavel M. Vassiliev
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.4
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    • pp.345-359
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    • 2024
  • Deposition of extracellular matrix (ECM) in the trabecular meshwork (TM) increases aqueous humour outflow resistance leading to elevation of intraocular pressure (IOP) in primary open-angle glaucoma, which remains the only modifiable risk factor. Resveratrol has been shown to counteract the steroid-induced increase in IOP and increase the TM expression of ECM proteolytic enzymes; however, its effects on the deposition of ECM components by TM and its associated pathways, such as TGF-β-SMAD signalling remain uncertain. This study, therefore, explored the effects of trans-resveratrol on the expression of ECM components, SMAD signalling molecules, plasminogen activator inhibitor-1 and tissue plasminogen activator in dexamethasone-treated human TM cells (HTMCs). We also studied the nature of molecular interaction of trans-resveratrol with SMAD4 domains using ensemble docking. Treatment of HTMCs with 12.5 µM trans-resveratrol downregulated the dexamethasone-induced increase in collagen, fibronectin and α-smooth muscle actin at gene and protein levels through downregulation of TGF-β1, SMAD4, and upregulation of SMAD7. Downregulation of TGF-β1 signalling by trans-resveratrol could be attributed to its effect on the transcriptional activity due to high affinity for the MH2 domain of SMAD4. These effects may contribute to resveratrol's IOP-lowering properties by reducing ECM deposition and enhancing aqueous humour outflow in the TM.

Detection of Benzene Metabolite Induced Aneuploidy and Translocation in HL-60 Cells by Fluorescence in situ Hybridization using Whole Chromosome-specific Probes for Chromosome 8 and 21 (벤젠 대사산물에 의해 유도된 HL-60 세포의 8번 및 21번 염색체의 이수성 및 상호전좌)

  • 김수영;정해원
    • Environmental Mutagens and Carcinogens
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    • v.22 no.2
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    • pp.90-96
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    • 2002
  • Benzene is a widespread human carcinogen, inducing leukemia and hematotoxicity. Exposure to benzene metabolites has been shown to cause genetic damage, including aneusomy and chromosome aberrations. Fluorescence in situ hybridization(FISH) procedure was used to determine if the benzene metabolite, 1, 2, 4-benzenetriol(BT), hydroquinone(HQ) and trans, trans-muconic acid(t,t-MA) induced specific chromosomal change in HL-60 cells. Treatment with BT, HQ and t,t-MA resulted in the induction of monosomy 8 and 21 in HL-60 cells in a dose-dependent manner. All of these metabolites also induced trisomy 8 and 21, but no correlation between frequencies of trisomy and concentration was found. Translocations between chromosome 8 and another unidentified chromosome [t(8:\ulcorner)], and between chromosome 21 and another unidentified chromosome [t(8:21)] were found. However, translocation between chromosome 8 and 21 [t(8:21)] was not found. Results indicate that the benzene metabolites, BT, HQ and t,t-MA, induce chromosome specific numerical and structural aberrations, and the fluorescence in situ hybridization (FISH) approach may be a useful and powerful technique for detection of aneuploidy.

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Ribozyme-Mediated Replacement of p53 RNA by Targeted Trans-Splicing

  • Shin, Kyung-Sook;Bae, Soo-Jin;Hwang, Eun-Seong;Jeong, Sun-Joo;Lee, Seong-Wook
    • Journal of Microbiology and Biotechnology
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    • v.12 no.5
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    • pp.844-848
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    • 2002
  • In more than half of human tumors, the p53 tumor suppressor gene is mutated. Thus, restoration of wild-type p53 activity by repair of mutant RNA could be a potentially promissing approach to cancer treatment. To explore the potential use of RNA repair for cancer therapy, trans-splicing group I ribozymes were developed that could replace mutant p53 RNA with RNA sequence attached to the 3'end of ribozymes. By employing a mapping library of ribozymes, we first determined which regions of the p53 RNA are accessible to ribozymes, and found that the leader sequences upstream of the AUG start codon appeared to be particularly accessible. Next, trans-splicing ribozymes were generated that specifically recognized the sequences around these accessible regions. Subsequently, the ribozymes reacted with and altered the p53 transcripts by transferring a 3'exon tag sequence onto the targeted p53 RNA with high fidelity. Thus, these ribozymes could be utilized to repair mutant p53 in tumors, which would revert the neoplastic phenotype.

Changes in Carotenoids Contents in Pureed and Cooked Carrot and Spinach during Storage (가열처리 및 저장조건에 따른 당근과 시금치퓨레의 Carotenoids 함량변화와 이성질화 형성에 관한 연구)

  • ;;Robert M, Russell
    • Korean journal of food and cookery science
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    • v.19 no.1
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    • pp.83-95
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    • 2003
  • Investigations were conducted on the changes in carotenoids content, and quantification of cis-trans-${\beta}$-carotene Isomers in pureed and cooked carrot and spinach during storage. The isomerization and degradation of carotenoids were monitored by high-performance liquid chromatography on a C$\_$30/ reversed-phase column with diode-array detection. The results showed that lutein, ail-trans-${\beta}$-carotene, ${\alpha}$-carotene, 9-cis-${\beta}$-carotene and 13-cis-${\beta}$-carotene were present in carrot and spinach. Zeaxanthin and cryptoxanthin were present in raw spinach. The contents of lutein, zeaxanthin, cryptoxanthin, ${\alpha}$-carotene and all-trans-${\beta}$-carotene in pureed and cooked carrot and spinach decreased with increasing storage period. The 9-cis and 13-cis carotenoid isomers were the major types formed in cooked carrot during storage. Cooking was not found to alter the carotenoid profile of the sample, but increased the total amount of carotenoids compared with pured ones. This increase could be explained that cooking itself increased the extraction efficiency and inactivated the enzymes degradating carotenoids.

Cancer Cell Targeting with Mouse TERT-Specific Group I Intron of Tetrahymena thermophila

  • Ban, Gu-Yee;Song, Min-Sun;Lee, Seong-Wook
    • Journal of Microbiology and Biotechnology
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    • v.19 no.9
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    • pp.1070-1076
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    • 2009
  • Telomerase reverse transcriptase (TERT), which prolongs the replicative life span of cells, is highly upregulated in 85-90% of human cancers, whereas most normal somatic tissues in humans express limited levels of the telomerase activity. Therefore, TERT has been a potential target for anticancer therapy. Recently, we described a new approach to human cancer gene therapy, which is based on the group I intron of Tetrahymena thermophila. This ribozyme can specifically mediate RNA replacement of human TERT (hTERT) transcript with a new transcript harboring anticancer activity through a trans-splicing reaction, resulting in selective regression of hTERT-positive cancer cells. However, to validate the therapeutic potential of the ribozyme in animal models, ribozymes targeting inherent transcripts of the animal should be developed. In this study, we developed a Tetrahymena-based trans-splicing ribozyme that can specifically target and replace the mouse TERT (mTERT) RNA. This ribozyme can trigger transgene activity not only also in mTERT-expressing cells but hTERT-positive cancer cells. Importantly, the ribozyme could selectively induce activity of the suicide gene, a herpes simplex virus thymidine kinase gene, in cancer cells expressing the TERT RNA and thereby specifically hamper the survival of these cells when treated with ganciclovir. The mTERT-targeting ribozyme will be useful for evaluation of the RNA replacement approach as a cancer gene therapeutic tool in the mouse model with syngeneic tumors.