• Title/Summary/Keyword: A4

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Protein phosphatase 4 dephosphorylates phosphofructokinase-1 to regulate its enzymatic activity

  • Jaehong Park;Dong-Hyun Lee
    • BMB Reports
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    • v.56 no.11
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    • pp.618-623
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    • 2023
  • Most cancer cells utilize glucose at a high rate to produce energy and precursors for the biosynthesis of macromolecules such as lipids, proteins, and nucleic acids. This phenomenon is called the Warburg effect or aerobic glycolysis- this distinct characteristic is an attractive target for developing anticancer drugs. Here, we found that Phosphofructokinase-1 (PFK-1) is a substrate of the Protein Phosphatase 4 catalytic subunit (PP4C)/PP4 regulatory subunit 1 (PP4R1) complex by using immunoprecipitation and in vitro assay. While manipulation of PP4C/PP4R1 does not have a critical impact on PFK-1 expression, the absence of the PP4C/PP4R1 complex increases PFK-1 activity. Although PP4C depletion or overexpression does not cause a dramatic change in the overall glycolytic rate, PP4R1 depletion induces a considerable increase in both basal and compensatory glycolytic rates, as well as the oxygen consumption rate, indicating oxidative phosphorylation. Collectively, the PP4C/PP4R1 complex regulates PFK-1 activity by reversing its phosphorylation and is a promising candidate for treating glycolytic disorders and cancers. Targeting PP4R1 could be a more efficient and safer strategy to avoid pleiotropic effects than targeting PP4C directly.

A Cyclin-Dependent Kinase Inhibitor, p16^{INK4A}, Induces Apoptosis in The Human Cancer Cells. (Cyclin-dependent Kinase저해 단백질 p16^{INK4A}의 인체 암세포에서의 세포사멸 유도 활성)

  • 김민경;이철훈
    • Microbiology and Biotechnology Letters
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    • v.32 no.1
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    • pp.72-77
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    • 2004
  • Previously, we synthesized a novel Cyclin-dependent kinase inhibitor, MCS-5A. Also, we investigated the involvement of cell cycle regulatory events during MCS-5A-mediated apoptosis in HL-60(+p16/-p53) cells with up-regulation of p16 protein expression. In contrast, apoptosis was not observed in A549(-p16/+p53) cells. Therefore we propose that $p16^{INK4A}$ is a key enzyme for inducing apoptosis. In the present studies, we have explored the mechanism of $p16^{INK4A}$ -mediated cytotoxicity and the role of p16.sup INK4A/ overexpression in the induction of apoptosis in human tumor cells. The tumor suppressor gene $p16^{INK4A}$ is known as a cyclin-dependent kinase inhibitor (CKI) and cell cycle regulator. We expressed wild type $p16^{INK4A}$ in pcDNA3.1 vector and then transfected into non-small cell lung cancer (NSCLC) cell expressing different statue of p16$^{INK4A}$, p53 gene〔A549(-p16/+p53), H1299(-p16/-p53) and HeLa(+pl6/+p53) cell line〕. TUNEL assay (including propidium iodide staining following transfection of these cell line with pcDNA3.1-pl6) indicate that p16$^{INK4A}$-mediated cytotoxicity was associated with apoptosis. This is supported by studies demonstrating an induction of caspase 3 cleavage due to the transfection of A549, H1299 and HeLa cells with pcDNA3.1-pl6. These results suggest that p16$^{INK4A}$ has a new function of inducing apoptosis which is not related with the function of tumor suppressor gene p53.

Acanthamoeba sohi, n. sp., a pathogenic Korean isolate YM-4 from a freshwater fish

  • Im, Kyung-Il;Shin, Ho-Joon
    • Parasites, Hosts and Diseases
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    • v.41 no.4
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    • pp.181-188
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    • 2003
  • A new species of Acanthamoeba was isolated from a freshwater fish in Korea and tentatively named Acanthamoeba sp. YM-4 (Korean isolate YM-4). The trophozoites were $11.0-23.0{\;}{\mu\textrm{m}}$ in length and had hyaline filamentous projections. Cysts were similar to those of A. culbertsoni and A. royreba, which were previously designated as Acanthamoeba group III. Acanthamoeba YM-4 can survive at $40^{\circ}C$, and its generation time was 19.6 hr, which was longer than that of A. culbertsoni. In terms of the in vitro cytotoxicity of lysates, Acanthamoeba YM-4 was weaker than A. culbertsoni, but stronger than A. polyphaga. On the basis of the mortality of experimentally infected mice, Acanthamoeba YM-4 was found to be highly virulent. The isoenzymes profile of Acanthamoeba YM-4 was similar to that of A. royreba. An anti-Acanthamoeba YM-4 monoclonal antibody, McAY7, was found to react only with Acanthamoeba YM-4, and not with A. culbertsoni. Random amplified polymorphic DNA marker analysis and RFLP analysis of mitochondrial DNA and of 18S small subunit ribosomal RNA, placed Acanthamoeba YM-4 in a separate cluster on the basis of phylogenetic distances. Thus the Acanthamoeba Korean isolate YM-4 was identified as a new species, and assigned as Acanthamoeba sohi.

Histone Deacetylase Inhibitor Stimulate CYP3A4 Proximal Promoter Activity in HepG2 Cells

  • Kim Ja Young;Ahn Mee Ryung;Kim Dae-Kee;Sheen Yhun Yhong
    • Archives of Pharmacal Research
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    • v.27 no.4
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    • pp.407-414
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    • 2004
  • The expression of CYP3A4 gene is induced by a variety of structurally unrelated xenobiotics including the antibiotic rifampicin, pregnenolone 16-carbonitrile (PCN), and endogenous hormones, that might mediate through steroid and xenobiotic receptor (SXR) system. The molecular mechanisms underlying regulation of CYP3A4 gene expression have not been understood. In order to gain the insight of the molecular mechanism of CYP3A4 gene expression, study has been undertaken to investigate if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter in human hepatoma HepG2 cells. Also we have investigated to see if SXR is involved in the regulation of CYP3A4 proximal promoter activity in human hepatoma HepG2 cells. HepG2 cells were transfected with a plasmid PCYP3A4-Luc containing ${\~}1kb$ of the CYP3A4 proximal promoter region (-863 to +64 bp) in front of a reporter gene, luciferase, in the presence or absence of pSAP-SXR. In HepG2 cells, CYP3A4 inducers, such as rifampicin, PCN and RU486 showed minimal stimulation of CYP3A4 proximal promoter activity in the absence of SXR and histone deacetylase (HDAC) inhibitors. 4-Dimethylamino-H-[4-(2-hydroxycarbamoylvinyl)benzyl]benzamide (IN2001), a new class HDAC inhibitor significantly increased CYP3A4 proximal promoter activity over untreated control cells and rifampicin concomitant treatment with IN2001 increased further CYP3A4 proximal promoter activity that was stimulated by IN2001 The results of this study demon-strated that both HDAC inhibitors and SXR are essential to increase of CYP3A4 proximal promoter activity by CYP3A4 inducers such as PCN, rifampicin, and RU486. Especially SXR seems to be important for the dose dependent response of CYP3A4 inducing chemicals to stimulate CYP3A4 proximal promoter activity. Also this data suggested that HDAC inhibitors seemed to facilitate the CYP3A4 proximal promoter to be activated by chemicals.

Hydration Properties of 3CaO.3A12O3.CaSO4.CaSO4ㆍ2H2O - Ca(OH)24 - 3CaO.Al2O3 System (3CaO.3A12O3.CaSO4.CaSO4.2H2O - Ca(OH)24 - 3CaO.Al2O3계의 수화 특성)

  • 배승훈;송종택
    • Journal of the Korean Ceramic Society
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    • v.40 no.9
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    • pp.859-866
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    • 2003
  • When calcium sulfoaluminate-based expansive cement was hydrated, ettringite and monosulfate were mainly formed. The crack of hardened cement was prevented by compensating drying shrinkage due to formation of the above hydrates. In order to study the hydration properties of calcium sulfoaluminate-based expanding cement, 3CaOㆍ3Al$_2$O$_3$ㆍCaSO$_4$(C$_4$A$_3$S) was prepared by chemical synthesis, and then the hydration of $C_4$A$_3$S-Ca(OH)$_2$-CaSO$_4$.$2H_2O$-C$_3$A system_was characterized. Good $C_4$A$_3$S phase was prepared at $1300^{\circ}C$ by chemical synthesis, and the main hydration product of $C_4$A$_3$S-Ca(OH)$_2$-CaSO$_4$.2$H_2O$ system was ettringite. In the case of hydration $C_4$A$_3$S-Ca(OH)$_2$-CaSO$_4$ㆍ 2$H_2O$-C$_3$A system, ettringite was formed in the early period and it was transformed into monosulfate while consumed gypsum.

Added Value of the Sliding Sign on Right Down Decubitus CT for Determining Adjacent Organ Invasion in Patients with Advanced Gastric Cancer (진행성 위암 환자에서 인접 장기 침범을 결정하기 위한 우측와위 CT에서의 미끄러짐 징후의 추가적 가치)

  • Kyutae Jeon;Se Hyung Kim;Jeongin Yoo;Se Woo Kim
    • Journal of the Korean Society of Radiology
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    • v.83 no.6
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    • pp.1312-1326
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    • 2022
  • Purpose To investigate the added value of right down decubitus (RDD) CT when determining adjacent organ invasion in cases of advanced gastric cancer (AGC). Materials and Methods A total of 728 patients with pathologically confirmed T4a (pT4a), surgically confirmed T4b (sT4b), or pathologically confirmed T4b (pT4b) AGCs who underwent dedicated stomach-protocol CT, including imaging of the left posterior oblique (LPO) and RDD positions, were included in this study. Two radiologists scored the T stage of AGCs using a 5-point scale on LPO CT with and without RDD CT at 2-week intervals and recorded the presence of "sliding sign" in the tumors and adjacent organs and compared its incidence of appearance. Results A total of 564 patients (77.4%) were diagnosed with pT4a, whereas 65 (8.9%) and 99 (13.6%) patients were diagnosed with pT4b and sT4b, respectively. When RDD CT was performed additionally, both reviewers deemed that the area under the curve (AUC) for differentiating T4b from T4a increased (p < 0.001). According to both reviewers, the AUC for differentiating T4b with pancreatic invasion from T4a increased in the subgroup analysis (p < 0.050). Interobserver agreement improved from fair to moderate (weighted kappa value, 0.296-0.444). Conclusion RDD CT provides additional value compared to LPO CT images alone for determining adjacent organ invasion in patients with AGC due to their increased AUC values and improved interobserver agreement.

The DSTM TEP for IPv4 and IPv6 Interoperability (IPv4/IPv6의 연동을 위한 DSTM TEP의 기능)

  • 진재경;최영지;민상원
    • Journal of KIISE:Computing Practices and Letters
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    • v.9 no.5
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    • pp.578-587
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    • 2003
  • The DSTM (Dual Stack Transition Mechanism), one of tunneling mechanism, is considered as the best solution in IPv4/IPv6 transition recently. The DSTM provides a method to assure IPv4/v6 connectivity based on 4over6 (IPv4-over-IPv6) tunneling and temporal allocation of a global IPv4 address to a host requiring such communication. A TEP (Tunnel End Point) operates as a border router between IPv6 domain and IPv4 Internet, which performs encapsulation and decapsulation of 4over6 tunneling packets to assure hi-directional forwarding between both networks. In this paper, we analyze basic standards of the IPv6 protocol. And, we design and implement a DSTM TEP daemon block. The TEP daemon analyzes a fevers tunneling packet that is forwarded by the DSTM node, establishes the TEP's 4over6 interface, and supplies communication between a DSTM and a IPv4-only node. Finally, we construct a DSTM testbed and measure performance of the DSTM TEP. Our observation results show that performance of TEP supports the DSTM service.

Synthesis and Biological Evaluation as a Potential Antifungal Allylamine Derivatives (항진균 알릴아민 유도체의 합성과 생물학적 평가)

  • 정병호;정순영
    • YAKHAK HOEJI
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    • v.48 no.4
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    • pp.254-260
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    • 2004
  • Structure-activity relationship studies of allylamine type of antimycotics were carried out to evaluate the effect of naphthyl and methyl portion of naftifine. Compounds with 2,4-difluorophenyl( 2a-5a), 2,5-difluorophenyl(2b-5b), 4-ethylphenyl(2c-5c), 2-hydroxyphenyl(2d-5d) and 2-methylnaphthyl(2e-5e) instead of naphthyl group with hydrogen(3a-3e), methyl(4a-4e), and ethyl(5a-5e) in the place of methyl in naftifine were synthesized and tested their in vitro anti-fungal activity against five different fungi. Eight compounds( 3a, 4a, 5a, 3d, 4d, 4d, 5d, 3e, and 4e) showed significant anti-fungal activity against T. mentagroPhytes. (E)-N-(3-Phenyl-2-propenyl)-2- hydroxy-benzenemethaneamine( 3d) displayed moderate antifungal activity against all five different fungi.

Trichostatin A, a Histone Deacetylase Inhibitor Stimulate CYP3A4 Proximal Promoter Activity in Hepa-I Cells

  • Ahn Mee Ryung;Kim Dae-Kee;Sheen Yhun Yhong
    • Archives of Pharmacal Research
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    • v.27 no.4
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    • pp.415-421
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    • 2004
  • Cytochrome P450 3A4 (CYP3A4) is the most abundant CYPs in human liver, comprising approximately $30\%$ of the total liver CYPs contents and is involved in the metabolism of more than $60\%$ of currently used therapeutic drugs. However, the molecular mechanisms underly-ing regulation of CYP3A4 gene expression have not been understood. Thus, this study has been carried out to gain the insight of the molecular mechanism of CYP3A4 gene expression, investigating if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter. Also SXR was investigated to see if they were involved in the regulation of CYP3A4 proximal promoter activity. Hepa-1 cells were transfected with a plasmid containing ${\~}1kb$ of the human CYP3A4 proximal promoter region (863 to +64 bp) cloned in front of a reporter gene, luciferase, in the presence or absence of SXR. Transfected cells were treated with CYP3A4 inducers such as rifampicin, PCN and RU 486, in order to examine the regulation of CYP3A4 gene expression in the presence or absence of trichostatin A (TSA). In Hepa-1 cells, CYP3A4 inducers increased modestly the luciferase activity when TSA was co-treated, but this increment was not enhanced by SXR cotransfection. Taken together, these results indicated that the inhibition of histone deacetylation was required to SXR-mediated increase in CYP3A4 proximal promoter region when rifampicin, or PCN was treated. Further a trans-activation by SXR may demand other species-specific transcription factors.