• Title/Summary/Keyword: Cellular pathway

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Cloning and Expression of a Farnesyl Diphosphate Synthase in Centella asiatica (L.) Urban

  • Kim, Ok Tae;Ahn, Jun Cheul;Hwang, Sung Jin;Hwang, Baik
    • Molecules and Cells
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    • v.19 no.2
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    • pp.294-299
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    • 2005
  • A cDNA encoding farnesyl diphosphate synthase (FPS; EC2.5.1.1/EC2.5.1.10) was isolated from Centella asiacita (L.) Urban, using degenerate primers based on two highly conserved domains. A full-length cDNA clone was subsequently isolated by rapid amplification of cDNA ends (RACE) PCR. The sequence of the CaFPS (C. asiatica farnesyl diphosphate synthase) cDNA contains an open reading frame of 1029 nucleotides encoding 343 amino acids with a molecular mass of 39.6 kDa. The deduced CaFPS amino acid sequence exhibits 84, 79, and 72%, identity to the FPSs of Artemisia annua, Arabidopsis thaliana, and Oryza sativa, respectively. Southern blot analysis suggested that the C. asiatica genome contains only one FPS gene. An artificially expressed soluble form of the CaFPS was identified by SDS-PAGE. It had high specific activity and produced farnesyl diphosphate as the major isoprenoid.

A Forward Genetic Approach for Analyzing the Mechanism of Resistance to the Anti-Cancer Drug, 5-Fluorouracil, Using Caenorhabditis elegans

  • Kim, Seongseop;Shim, Jaegal
    • Molecules and Cells
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    • v.25 no.1
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    • pp.119-123
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    • 2008
  • Pyrimidine antagonists including 5-Fluorouracil (5-FU) have been used in chemotherapy for cancer patients for over 40 years. 5-FU, especially, is a mainstay treatment for colorectal cancer. It is a pro-drug that is converted to the active drug via the nucleic acid biosynthetic pathway. The metabolites of 5-FU inhibit normal RNA and DNA function, and induce apoptosis of cancer cells. One of the major obstacles to successful chemotherapy is the resistance of cancer cells to anti-cancer drugs. Therefore, it is important to elucidate resistance mechanisms to improve the efficacy of chemotherapy. We have used C. elegans as a model system to investigate the mechanism of resistance to 5-FU, which induces germ cell death and inhibits larval development in C. elegans. We screened 5-FU resistant mutants no longer arrested as larvae by 5-FU. We obtained 18 mutants out of 72,000 F1 individuals screened, and mapped them into three complementation groups. We propose that C. elegans could be a useful model system for studying mechanisms of resistance to anti-cancer drugs.

Mechanism, Function and Regulation of Microtubule-Dependent Microtubule Amplification in Mitosis

  • Zhu, Hui;Fang, Kayleen;Fang, Guowei
    • Molecules and Cells
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    • v.27 no.1
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    • pp.1-3
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    • 2009
  • Mitotic spindle mediates the segregation of chromosomes in the cell cycle and the proper function of the spindle is crucial to the high fidelity of chromosome segregation and to the stability of the genome. Nucleation of microtubules (MTs) from centrosomes and chromatin represents two well-characterized pathways essential for the assembly of a dynamic spindle in mitosis. Recently, we identified a third MT nucleation pathway, in which existing MTs in the spindle act as a template to promote the nucleation and polymerization of MTs, thereby efficiently amplifying MTs in the spindle. We will review here our current understanding on the molecular mechanism, the physiological function and the cell-cycle regulation of MT amplification.

Up-regulation of Early Growth Response-1 Expression by Endoplasmic Reticulum Stress

  • Han, Song-Yi;Kwon, Ki-Sang;Yun, Eun-Young;Goo, Tae-Won;Kwon, O-Yu
    • Biomedical Science Letters
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    • v.13 no.2
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    • pp.157-160
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    • 2007
  • Endoplasmic reticulum (ER) plays formation of disulfide bonds and proper folding of secretory proteins. Cellular responses to ER stress enhances the stress-activated kinase pathway and the induces a lot of immediate-early genes. Among of them, the early growth response-1 (Egr-1), a transcription factor, which plays an important role in cell growth, development, differentiation, apoptosis and various types of injury. For that reason, we have tested the expression of Egr-1 against ER stress inducible drugs (tunicamycin, DTT, A23187 and BFA) to understand what kind of aspect occurred by ER stresses.

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Current Advancement of Oral Cancer Research and its Clinical Implications (구강암의 연구동향 및 임상적 의의)

  • Kwon, Tae-Geon;Kim, Chin-Soo
    • The Journal of the Korean dental association
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    • v.48 no.8
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    • pp.576-586
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    • 2010
  • Recent advancement in molocular biology enhanced further understanding of the carcinogenesis of oral cancer and its relation with various genetic backgrounds. Familial risk factors includes similar habits of the family and polymorphic variations of the genes. Recently, human papilloma virus has been suggested to be linked with oral cancer progression. Enhancement of understanding of the damage or alteration in molecular pathway in various cellular response of oral cancer progression would lead the targeted therapy or precise early diagnosis of the oral cancer.

Phagocytic Roles of Glial Cells in Healthy and Diseased Brains

  • Jung, Yeon-Joo;Chung, Won-Suk
    • Biomolecules & Therapeutics
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    • v.26 no.4
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    • pp.350-357
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    • 2018
  • Glial cells are receiving much attention since they have been recognized as important regulators of many aspects of brain function and disease. Recent evidence has revealed that two different glial cells, astrocytes and microglia, control synapse elimination under normal and pathological conditions via phagocytosis. Astrocytes use the MEGF10 and MERTK phagocytic pathways, and microglia use the classical complement pathway to recognize and eliminate unwanted synapses. Notably, glial phagocytosis also contributes to the clearance of disease-specific protein aggregates, such as ${\beta}$-amyloid, huntingtin, and ${\alpha}$-synuclein. Here we reivew recent findings showing that glial cells are active regulators in brain functions through phagocytosis and that changes in glial phagocytosis contribute to the pathogenesis of various neurodegenerative diseases. A better understanding of the cellular and molecular mechanisms of glial phagocytosis in healthy and diseased brains will greatly improve our current approach in treating these diseases.

Increased Gene Expression in Cultured BEAS-2B Cells Treated with Metal Oxide Nanoparticles

  • Park, Eun-Jung;Park, Kwang-Sik
    • Toxicological Research
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    • v.25 no.4
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    • pp.195-201
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    • 2009
  • Recent publications showed that metal nanoparticles which are made from $TiO_2,\;CeO_2,\;Al_2O_3,\;CuCl_2,\;AgNO_3$ and $ZnO_2$ induced oxidative stress and pro-inflammatory effects in cultured cells and the responses seemed to be common toxic pathway of metal nanoparticles to the ultimate toxicity in animals as well as cellular level. In this study, we compared the gene expression induced by two different types of metal oxide nanoparticles, titanium dioxide nanoparticles (TNP) and cerium dioxide nanoparticles (CNP) using microarray analysis. About 50 genes including interleukin 6, interleukin 1, platelet-derived growth factor $\beta$, and leukemia inhibitory factor were induced in cultured BEAS2B cells treated with TNP 40 ppm. When we compared the induction levels of genes in TNP-treated cells to those in CNP-treated cells, the induction levels were very correlated in various gene categories (r=0.645). This may suggest a possible common toxic mechanism of metal oxide nanoparticles.

Regulation of $Ca^{2+}$ Signaling in Pulmonary Hypertension

  • Firth, Amy L.;Won, Jun Yeon;Park, Won Sun
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.1
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    • pp.1-8
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    • 2013
  • Understanding the cellular and molecular mechanisms involved in the development and progression of pulmonary hypertension (PH) remains imperative if we are to successfully improve the quality of life and life span of patients with the disease. A whole plethora of mechanisms are associated with the development and progression of PH. Such complexity makes it difficult to isolate one particular pathway to target clinically. Changes in intracellular free calcium concentration, the most common intracellular second messenger, can have significant impact in defining the pathogenic mechanisms leading to its development and persistence. Signaling pathways leading to the elevation of $[Ca^{2+}]_{cyt}$ contribute to pulmonary vasoconstriction, excessive proliferation of smooth muscle cells and ultimately pulmonary vascular remodeling. This current review serves to summarize the some of the most recent advances in the regulation of calcium during pulmonary hypertension.

An overview of the endocrine functions of osteocalcin

  • Baek, Kyunghwa
    • International Journal of Oral Biology
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    • v.44 no.4
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    • pp.125-129
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    • 2019
  • Osteocalcin is the most abundant non-collagenous protein produced in bone. It has traditionally been regarded as a marker of bone turnover and is thought to act in the bone matrix to regulate mineralization. However, emerging knowledge regarding osteocalcin has expanded to include functions in energy metabolism, fertilization, and regulation of cognition. Fully carboxylated osteocalcin binds to hydroxyapatite, thereby modulating bone turnover, whereas undercarboxylated osteocalcin in the circulation binds to osteocalcin-sensing receptors and acts as a hormone that affects multiple physiological aspects. In this review, we summarize the current knowledge regarding the hormonal actions of osteocalcin in various organs and potential cellular downstream signaling pathway that may be involved.

Intracellular Trafficking of Transferrin-Conjugated Liposome/DNA Complexes by Confocal Microscopy

  • Lee Sang Mi;Kim Jin-Seok
    • Archives of Pharmacal Research
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    • v.28 no.1
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    • pp.93-99
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    • 2005
  • Intracellular trafficking of transferrin-conjugated dimethyldioctadecyl-ammonium bromide liposome $(T_f-liposome)/DNA$ complexes in HeLa cells was studied using the double-labeled fluorescence technique and confocal microscopy. The size of the $T_f-liposome/DNA$ complex was about 367 nm in diameter and the zeta-potential of it at a 5:1 (w/w) ratio was almost neutral. The intracellular pathway of the $T_f-liposome/DNA$ complex, noted as green (FITC), red (rhodamine) or yellow (FITC + rhodamine) fluorescence, was elucidated from the plasma membrane to the endosome (or lysosome), and finally to the nucleus. The results of this study indicate that plasmid DNA enters into the nucleus not only as a free form but as an associated form complexed with $T_f-liposome$. More interestingly, the $T_f-liposome$ undergoes a nuclear location in the form of ordered structures. This could be a very useful piece of information in designing a safe and advanced gene delivery system.