• 제목/요약/키워드: Cellular pathway

검색결과 935건 처리시간 0.031초

Gene Expression Profiling Reveals that Paeoniflorin Has an Apoptotic Potential in Human Leukemia U937 Cells

  • Lim, Soo-Hyun;Ahn, Kwang-Seok;Kim, Sung-Hoon;Jang, Hyeung-Jin
    • Molecular & Cellular Toxicology
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    • 제5권4호
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    • pp.335-345
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    • 2009
  • A major source of paeoniflorin (PF) which was from the Paeonia lactiflora root, has been used as a herbal medicine in East Asia for its antiallergic, antiinflammatory, and immunoregulatory effects. However, only few details are known about the mechanism of apoptosis induced by this compound. The present study was undertaken to further elucidate the molecular mechanism of apoptosis and the changes of gene expression elicited by PF using DNA microarrays and computational gene-expression analysis tools in human leukemia U937 cells. A comparative global transcription analysis between treatment with PF and anisomycin (AM) that induces apoptosis in U937 cells revealed that c-Jun-$NH_2$-kinase (JNK) pathway related genes were less expressed in PF-treated cells. Elucidation of the mechanisms by which PF conducts its anti-cancer activities through comparative analysis of the gene expression is necessary to provide a solid foundation for its use as a promising agent in prevention and treatment strategies.

Accumulation of Flavonols in Response to Ultraviolet-B Irradiation in Soybean Is Related to Induction of Flavanone 3-β-Hydroxylase and Flavonol Synthase

  • Kim, Bong Gyu;Kim, Jeong Ho;Kim, Jiyoung;Lee, Choonghwan;Ahn, Joong-Hoon
    • Molecules and Cells
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    • 제25권2호
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    • pp.247-252
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    • 2008
  • There are several branch points in the flavonoid synthesis pathway starting from chalcone. Among them, the hydroxylation of flavanone is a key step leading to flavonol and anthocyanin. The flavanone 3-${\beta}$-hydroxylase (GmF3H) gene was cloned from soybean (Glycine max cultivar Sinpaldal) and shown to convert eriodictyol and naringenin into taxifolin and dihydrokaempferol, respectively. The major flavonoids in this soybean cultivar were found by LC-MS/MS to be kamepferol O-triglycosides and O-diglycosides. Expression of GmF3H and flavonol synthase (GmFLS) was induced by ultraviolet-B (UV-B) irradiation and their expression stimulated accumulation of kaempferol glycones. Thus, GmF3H and GmFLS appear to be key enzymes in the biosynthesis of the UV-protectant, kaempferol.

Arabidopsis Histidine-containing Phosphotransfer Factor 4 (AHP4) Negatively Regulates Secondary Wall Thickening of the Anther Endothecium during Flowering

  • Jung, Kwang Wook;Oh, Seung-Ick;Kim, Yun Young;Yoo, Kyoung Shin;Cui, Mei Hua;Shin, Jeong Sheop
    • Molecules and Cells
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    • 제25권2호
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    • pp.294-300
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    • 2008
  • Cytokinins are essential hormones in plant development. $\underline{A}$rabidopsis $\underline{h}$istidine-containing $\underline{p}$hosphotransfer proteins (AHPs) are mediators in a multistep phosphorelay pathway for cytokinin signaling. The exact role of AHP4 has not been elucidated. In this study, we demonstrated young flower-specific expression of AHP4, and compared AHP4-overexpressing (Ox) trangenic Arabidopsis lines and an ahp4 knock-out line. AHP4-Ox plants had reduced fertility due to a lack of secondary cell wall thickening in the anther endothecium and inhibition of IRREGURAR XYLEMs (IRXs) expression in young flowers. Conversely, ahp4 anthers had more lignified anther walls than the wild type, and increased IRXs expression. Our study indicates that AHP4 negatively regulates thickening of the secondary cell wall of the anther endothecium, and provides new insight into the role of cytokinins in formation of secondary cell walls via the action of AHP4.

Post-Translational Regulation of miRNA Pathway Components, AGO1 and HYL1, in Plants

  • Cho, Seok Keun;Ryu, Moon Young;Shah, Pratik;Poulsen, Christian Peter;Yang, Seong Wook
    • Molecules and Cells
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    • 제39권8호
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    • pp.581-586
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    • 2016
  • Post-translational modifications (PTMs) of proteins are essential to increase the functional diversity of the proteome. By adding chemical groups to proteins, or degrading entire proteins by phosphorylation, glycosylation, ubiquitination, neddylation, acetylation, lipidation, and proteolysis, the complexity of the proteome increases, and this then influences most biological processes. Although small RNAs are crucial regulatory elements for gene expression in most eukaryotes, PTMs of small RNA microprocessor and RNA silencing components have not been extensively investigated in plants. To date, several studies have shown that the proteolytic regulation of AGOs is important for host-pathogen interactions. DRB4 is regulated by the ubiquitin-proteasome system, and the degradation of HYL1 is modulated by a de-etiolation repressor, COP1, and an unknown cytoplasmic protease. Here, we discuss current findings on the PTMs of microprocessor and RNA silencing components in plants.

Alterations in Striatal Circuits Underlying Addiction-Like Behaviors

  • Kim, Hyun Jin;Lee, Joo Han;Yun, Kyunghwa;Kim, Joung-Hun
    • Molecules and Cells
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    • 제40권6호
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    • pp.379-385
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    • 2017
  • Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.

AMP-activated protein kinase 활성화 기전과 관련 약물의 효과 (Effects of AMP-activated Protein Kinase Activating Compounds and Its Mechanism)

  • 최형철
    • Journal of Yeungnam Medical Science
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    • 제29권2호
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    • pp.77-82
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    • 2012
  • AMP-activated protein kinase (AMPK) is an important cellular fuel sensor. Its activation requires phosphorylation at Thr-172, which resides in the activation loop of the ${\alpha}1$ and ${\alpha}2$ subunits. Several AMPK upstream kinases are capable of phosphorylating AMPK at Thr-172, including LKB1 and CaMKK${\beta}$ ($Ca^{2+}$/calmodulin-dependent protein kinase kinase${\beta}$). AMPK has been implicated in the regulation of physiological signals, such as in the inhibition of cholesterol fatty acid, and protein synthesis, and enhancement of glucose uptake and blood flow. AMPK activation also exhibits several salutary effects on the vascular function and improves vascular abnormalities. AMPK is modulated by numerous hormones and cytokines that regulate the energy balance in the whole body. These hormone and cytokines include leptin, adiponectin, ghrelin, and even thyroid hormones. Moreover, AMPK is activated by several drugs and xenobiotics. Some of these are in being clinically used to treat type 2 diabetes (e.g., metformin and thiazolidinediones), hypertension (e.g., nifedipine and losartan), and impaired blood flow (e.g., aspirin, statins, and cilostazol). I reviewed the precise mechanisms of the AMPK activation pathway and AMPK-modulating drugs.

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Roles of Signaling Pathways in the Epithelial-Mesenchymal Transition in Cancer

  • Liu, Xia;Yun, Fen;Shi, Lin;Li, Zhe-Hai;Luo, Nian-Rong;Jia, Yong-Feng
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권15호
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    • pp.6201-6206
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    • 2015
  • The epithelial-mesenchymal transition (EMT) is a cellular process though which an epithelial phenotype can be converted into a phenotype of mesenchymal cells. Under physiological conditions EMT is important for embryogenesis, organ development, wound repair and tissue remodeling. However, EMT may also be activated under pathologic conditions, especially in carcinogenesis and metastatic progression. Major signaling pathways involved in EMT include transforming growth factor ${\beta}(TGF-{\beta})$, Wnt, Notch, Hedgehog and other signaling pathways. These pathways are related to several transcription factors, including Twist, Smads and zinc finger proteins snail and slug. These interact with each other to provide crosstalk between the relevant signaling pathways. This review lays emphasis on studying the relationship between EMT and signaling pathways in carcinogenesis and metastatic progression.

인슐린 매개성 Microsomal Epoxide Hydrolase의 발현증가에서 Akt의 역할 (Role of Akt in Insulin-Mediated Increase in Expression of Microsomal Epoxide Hydrolase)

  • 김상겸;김봉희;오정민;윤강욱;김충현;강건욱
    • 약학회지
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    • 제51권5호
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    • pp.291-295
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    • 2007
  • The present study examines the effect of dominant-negative Akt on the insulin-mediated microsomal epoxide hydrolase (mEH) induction in rat hepatocytes. We also assessed the role of insulin in the expression of soluble epoxide hydrrolase (sEH). Insulin increased mEH levels and the enzyme activities, whereas sEH protein expression was unaffected by insulin. The specific PI3K inhibitors or p70 S6 kinase inhibitor ameliorated the insulin-mediated increase in mEH protein levels. Infection with adenovirus expressing dominant-negative and kinase-dead mutant of Akt1 effectively inhibited the insulin-mediated increase in mEH expression and mEH activity. These results suggest that mEH and sEH are differentially regulated by insulin and PI3K/Akt/p70S6K are active in the insulin-mediated regulation of mEH expression.

Hologram Based QSAR Analysis of Caspase-3 Inhibitors

  • Sathya., B
    • 통합자연과학논문집
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    • 제11권2호
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    • pp.93-100
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    • 2018
  • Caspases, a family of cysteinyl aspartate-specific proteases plays a central role in the regulation and the execution of apoptotic cell death. Caspase-3 has been proven to be an effective target for reducing the amount of cellular and tissue damage because the activation of caspases-3 stimulates a signalling pathway that ultimately leads to the death of the cell. In this study, Hologram based Quantitative Structure Activity Relationship (HQSAR) models was generated on a series of Caspase-3 inhibitors named 3, 4-dihydropyrimidoindolones derivatives. The best HQSAR model was obtained using atoms, bonds, and hydrogen atoms (A/B/H) as fragment distinction parameter using hologram length 61 and 3 components with fragment size of minimum 5 and maximum 8. Significant cross-validated correlation coefficient ($q^2=0.684$) and non cross-validated correlation coefficients ($r^2=0.754$) were obtained. The model was then used to evaluate the eight external test compounds and its $r^2_{pred}$ was found to be 0.559. Contribution map show that presence of pyrrolidine sulfonamide ring and its bulkier substituent's makes big contributions for improving the biological activities of the compounds.

In silico analysis of MeJA-induced comparative transcriptomes in Brassica oleraceae L. var. capitata

  • Lee, Ok Ran;Kim, Dae-Soo
    • Journal of Plant Biotechnology
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    • 제43권2호
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    • pp.189-203
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    • 2016
  • Brassica oleraceae var capitata is a member of the Brassicaceae family and is widely used as an horticultural crop. In the present study, transcriptome analysis of B. oleraceae L. var capitata was done for the first time using eight-week old seedlings treated with $50{\mu}m$ MeJA, versus mock-treated samples. The complete transcripts for both samples were obtained using the GS-FLX sequencer. Overall, we obtained 275,570 and 266,457 reads from seedlings treated with or without $50{\mu}m$ MeJA, respectively. All the obtained reads were annotated using biological databases and functionally classified using gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomics (KEGG). By using GO analyses, putative transcripts were examined in terms of biotic and abiotic stresses, cellular component organization, biogenesis, and secondary metabolic processes. The KEGG pathways for most of the transcripts were involved in carbohydrate metabolism, energy metabolism, and secondary metabolite synthesis. In order to double the sequenced data, we randomly chose two putative genes involved in terpene biosynthetic pathways and studied their transcript patterns under MeJA treatment. This study will provide us a platform to further characterize the genes in B. oleracea var capitata.