• Title/Summary/Keyword: Cell division cycle

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Environmental factors affecting development of Aspergillus nidulans

  • Han, Kap-Hoon;Lee, Dong-Beom;Kim, Jong-Hak;Kim, Min-Su;Han, Kyu-Yong;Kim, Won-Shin;Park, Young-Soon;Kim, Heui-Baik;Han, Dong-Min
    • Journal of Microbiology
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    • v.41 no.1
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    • pp.34-40
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    • 2003
  • Aspergillus nidulans, a homothalic ascomycete, has a complete sexual reproductive cycle as well as an asexual one. Both sexual and asexual development are known to be genetically programmed, but are also strongly affected by environmental factors including nutrients, light, temperature and osmolarity. We have examined these factors to define favored conditions for fruiting body (cleistothecium) formation. In general, fruiting body formation was enhanced where carbon and nitrogen sources were sufficient. Limitation of C-source caused predominant asexual development while inhibiting sexual development. When higher concentrations of glucose were supplied, more cleistothecia were formed. Other carbon sources including lactose, galactose and glycerol made the fungus develop cleistothecia very well, whereas acetate caused asexual sporulation only. Organic nitrogen sources like casein hydrolysate and glycine, and an increase in nitrate or ammonium concentration also enhanced sexual development. In addition to nutrient effects, low levels of aerobic respiration, caused either by platesealing or treatment with various chemicals, favored sexual development. Carbon limitation, light exposure and a high concentration of salts promoted asexual development preferentially, suggesting that stress conditions may drive the cell to develop asexual sporulation while comfortable and wellnourished growth conditions favored sexual development.

Genetic Features of Lung Adenocarcinoma with Ground-Glass Opacity: What Causes the Invasiveness of Lung Adenocarcinoma?

  • Kim, Dohun;Lee, Jong-Young;Yoo, Jin Young;Cho, Jun Yeun
    • Journal of Chest Surgery
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    • v.53 no.5
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    • pp.250-257
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    • 2020
  • Background: Lung adenocarcinoma (LUAD) with ground-glass opacity (GGO) can become aggravated, but the reasons for this aggravation are not fully understood. The goal of this study was to analyze the genetic features and causes of progression of GGO LUAD. Methods: LUAD tumor samples and normal tissues were analyzed using an Illumina HiSeq 4000 system. After the tumor mutational burden (TMB) was calculated, the identified mutations were classified as those found only in GGO LUAD, those present only in nonGGO LUAD, and those common to both tissue types. Ten high-frequency genes were selected from each domain, after which protein interaction network analysis was conducted. Results: Overall, 227 mutations in GGO LUAD, 212 in non-GGO LUAD, and 48 that were common to both tumor types were found. The TMB was 8.8 in GGO and 7.8 in non-GGO samples. In GGO LUAD, mutations of FCGBP and SFTPA1 were identified. FOXQ1, IRF5, and MAGEC1 mutations were common to both types, and CDC27 and NOTCH4 mutations were identified in the non-GGO LUAD. Protein interaction network analysis indicated that IRF5 (common to both tissue types) and CDC27 (found in the non-GGO LUAD) had significant biological functions related to the cell cycle and proliferation. Conclusion: In conclusion, GGO LUAD exhibited a higher TMB than non-GGO LUAD. No clinically meaningful mutations were found to be specific to GGO LUAD, but mutations involved in the epithelial-mesenchymal transition or cell cycle were found in both tumor types and in non-GGO tissue alone. These findings could explain the non-invasiveness of GGO-type LUAD.

Analysis of Gene Expression Modulated by Indole-3-carbinol in Dimethylbenz[a]anthracene-induced Rat Mammary Carcinogenesis

  • Kang, Jin-Seok;Park, Han-Jin;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • v.5 no.3
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    • pp.222-229
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    • 2009
  • Our previous finding that pre-initiation treatment of indole-3-carbinol (I3C) represents a chemopreventive effect in dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis has prompted us to test the global expression of genes at an early stage. Rats were continuously fed 300 ppm I3C in their diet at 6 weeks of age and were injected with DMBA at 7 weeks of age, and were sacrificed at 8 weeks of age. Global gene expression analysis using oligonucleotide microarrays was conducted to detect altered genes in DMBA- or DMBA plus I3C-treated mammary glands. Altered genes were identified by fold changes of 1.2 and by t-test (P<0.05) from the log ratios of the hybridization intensity of samples between control (Group 1) and DMBA (Group 2), and from those of samples between DMBA (Group 2) and DMBA plus I3C (Group 3). From these genes, we chose altered genes that were up- or down-regulated by DMBA treatment and recovered to the control level by I3C treatment. For early stage of carcinogenesis, I3C treatment induced the recovery to normal levels of several genes including cell cycle pathway (cyclin B2, cell division cycle 2 homolog A), MAP signaling pathway (fibroblast growth factor receptor 1, platelet derived growth factor receptor, beta polypeptide), and insulin signaling (protein phosphatase 1, regulatory (inhibitor) subunit 3B and flotillin 2), which were up-regulated by DMBA treatment. In addition, I3C treatment induced the recovery to normal levels of several genes including those of MAPK signaling (transforming growth factor, beta receptor 1 and protein phosphatase 3, catalytic subunit, beta isoform), which were down-regulated by DMBA treatment. These results suggest that the targeting of these genes presents a possible approach for chemoprevention in DMBA-induced mammary carcinogenesis.

Methanol extract of Myelophycus caespitosus ameliorates oxidative stress-induced cytotoxicity in C2C12 murine myoblasts via activation of heme oxygenase-1

  • Cheol Park;Hyun Hwangbo;Min Ho Han;Jin-Woo Jeong;Suengmok Cho;Gi-Young Kim;Hye-Jin Hwang;Yung Hyun Choi
    • Fisheries and Aquatic Sciences
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    • v.26 no.1
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    • pp.35-47
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    • 2023
  • Myelophycus caespitosus, a brown alga belonging to genus Myelophycus, has been traditionally used as a food and medicinal resource in Northeastern Asia. However, few studies have been conducted on its pharmacological activity. In this study, we evaluated whether methanol extract of M. caespitosus (MEMC) could protect against oxidative damage caused by hydrogen peroxide (H2O2) in C2C12 murine myoblasts. Our results revealed that MEMC could suppress H2O2-induced growth inhibition and DNA damage while blocking the production of reactive oxygen species. In H2O2-treated cells, cell cycle progression was halted at the G2/M phase, accompanied by changes in expression of key cell cycle regulators. However, these effects were attenuated by MEMC. In addition, we found that MEMC protected cells from induction of apoptosis associated with mitochondrial impairment caused by H2O2 treatment. Furthermore, MEMC enhanced the phosphorylation of nuclear factor-erythroid-2 related factor 2 (Nrf2) and expression and activity of heme oxygenase-1 (HO-1) in H2O2-treaetd C2C12 myoblasts. However, such anti-apoptotic and cytoprotective effects of MEMC were greatly abolished by HO-1 inhibitor, suggesting that MEMC could increase Nrf2-mediated activity of HO-1 to protect C2C12 myoblasts from oxidative stress.

Expression of Endometriosis Related Genes in the Shed Endometrial Tissues from Menstrual Blood (생리혈에 존재하는 자궁내막조직에서 자궁내막증 관련 유전자의 발현 양상)

  • Park, Chan-Woo;Jun, Jin-Hyun;Koong, Mi-Kyoung;Song, In-Ok
    • Clinical and Experimental Reproductive Medicine
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    • v.34 no.4
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    • pp.275-283
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    • 2007
  • Objective: This study was performed to investigate the expressions of endometriosis related genes in shed endometrial tissues from menstrual blood of patients with or without endometriosis. Methods: The shed endometrial tissues were collected on 2$^{nd}$ or 3$^{rd}$ day of menstrual cycle with Wallace catheter in patients with endometriosis (n=16) and without endometriosis (n=26). The mRNA expressions of twelve kinds of endometriosis related genes were compared between two groups using semi-quantitative RT-PCR. Results: The collected shed endometrium was confirmed by histological observation. Expressions of telomerase, c-kit and aromatase mRNA were not detected by RT-PCR in shed endometrial tissues. The mRNA expressions of apoptosis related genes (fas, fas ligand, bcl-2, bax), stem cell factor, estrogen receptor-$\alpha$/$\alpha$, endometriosis protein-I and secretory leukocyte protease inhibitor gene were similar between shed endometrial tissues with endometriosis and without endometriosis. Conclusion: We could not find the difference of mRNA expressions of tested endometriosis related genes between shed endometrial tissues with or without endometriosis by semi-quantitative RT-PCR analysis. It may be related to the dynamical changes of gene expressions in the endometrium with menstrual cycle.

Stereoisomer-specific ginsenoside 20(S)-Rg3 reverses replicative senescence of human diploid fibroblasts via Akt-mTOR-Sirtuin signaling

  • Yang, Kyeong-Eun;Jang, Hyun-Jin;Hwang, In-Hu;Hong, Eun Mi;Lee, Min-Goo;Lee, Soon;Jang, Ik-Soon;Choi, Jong-Soon
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.341-349
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    • 2020
  • Background: The replicative senescence of human dermal fibroblasts (HDFs) is accompanied by growth arrest. In our previous study, the treatment of senescent HDFs with Rg3(S) lowered the intrinsic reactive oxygen species (ROS) levels and reversed cellular senescence by inducing peroxiredoxin-3, an antioxidant enzyme. However, the signaling pathways involved in Rg3(S)-induced senescence reversal in HDFs and the relatedness of the stereoisomer Rg3(R) in corresponding signaling pathways are not known yet. Methods: We performed senescence-associated β-galactosidase and cell cycle assays in Rg3(S)-treated senescent HDFs. The levels of ROS, adenosine triphosphate (ATP), and cyclic adenosine monophosphate (cAMP) as well as the mitochondrial DNA copy number, nicotinamide adenine dinucleotide (NAD)+/1,4-dihydronicotinamide adenine dinucleotide (NADH) ratio, and NAD-dependent sirtuins expression were measured and compared among young, old, and Rg3(S)-pretreated old HDFs. Major signaling pathways of phosphatidylinositol 3-kinase/Akt, 5' adenosine monophosphate-activated protein kinase (AMPK), and sirtuin 1/3, including cell cycle regulatory proteins, were examined by immunoblot analysis. Results: Ginsenoside Rg3(S) reversed the replicative senescence of HDFs by restoring the ATP level and NAD+/NADH ratio in downregulated senescent HDFs. Rg3(S) recovered directly the cellular levels of ROS and the NAD+/NADH ratio in young HDFs inactivated by rotenone. Rg3(S) mainly downregulated phosphatidylinositol 3-kinase/Akt through the inhibition of mTOR by cell cycle regulators like p53/p21 in senescent HDFs, whereas Rg3(R) did not alter the corresponding signaling pathways. Rg3(S)-activated sirtuin 3/PGC1α to stimulate mitochondrial biogenesis. Conclusion: Cellular molecular analysis suggests that Rg3(S) specifically reverses the replicative senescence of HDFs by modulating Akt-mTOR-sirtuin signaling to promote the biogenesis of mitochondria.

Modeling of the Cycle Life of a Lithium-ion Polymer Battery (리튬 이온 폴리머 전지의 사이클 수명 모델링)

  • Kim, Ui Seong;Lee, Jungbin;Yi, Jaeshin;Shin, Chee Burm;Choi, Je Hun;Lee, Seokbeom
    • Korean Chemical Engineering Research
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    • v.47 no.3
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    • pp.344-348
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    • 2009
  • One-dimensional modeling was carried-out to predict the capacity loss of a lithium-ion polymer battery during cycling. The model not only accounted for electrochemical kinetics and ionic mass transfer in a battery cell, but also considered the parasitic reaction inducing the capacity loss. In order to validate the modeling, modeling results were compared with the measurement data of the cycling behaviors of the lithium-ion polymer batteries having nominal capacity of 5Ah from LG Chem. The cycling was performed under the protocol of the constant current discharge and the constant current and constant voltage charge. The discharge rate of 1C was used. The range of state of charge was between 1 and 0.2. The voltage was kept constant at 4.2 V until the charge current tapered to 50 mA. The retention capacity of the battery was measured with 1C and 5C discharge rates before the beginning of cycling and after every 100 cycles of cycling. The modeling results were in good agreement with the measurement data.

Anti-oxidative and Anti-cancer Activities of Ethanol Extract of Litsea populifolia (인체 폐암 세포주 A549에서 Litsea populifolia 추출물의 항산화 및 항암활성 분석)

  • Jin, Soojung;Oh, You Na;Jeong, Hyun Young;Yun, Hee Jung;Park, Jung-ha;Kwon, Hyun Ju;Kim, Byung Woo
    • Journal of Life Science
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    • v.29 no.6
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    • pp.679-687
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    • 2019
  • Litsea populifolia, a plant species of the Lauraceae family, is widely distributed in the tropical and subtropical areas of Asia. The phylogenetic relationships and botanical characteristics of L. populifolia have been reported; however, its anti-oxidative and anti-cancer activities remain unclear. In this study, we evaluated the anti-oxidative and anti-cancer effects of ethanol extracts of L. populifolia (EELP) together with the molecular mechanism of its anti-cancer activity in human lung adenocarcinoma A549 cells. EELP showed significant anti-oxidative effects with a 50% inhibitory concentration at $11.71{\mu}g/ml$, which was measured by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. EELP exhibited cytotoxic activity and induced cell cycle arrest at the G1 phase in A549 cells in a dose-dependent manner, whereas EELP did not have the cytotoxic effect on the normal human lung cell line IMR90. Treatment with EELP also resulted in a decreased expression of G1/S transition-related molecules-including cyclin-dependent kinase (CDK) 2, CDK6, cyclin D1, and cyclin E-both for the transcription and translation levels. EELP-induced G1 arrest was associated with the phosphorylation of checkpoint kinase 2 (CHK2), p53, cell division cycle 25 homolog A (CDC25A), and the reduction of CDC25A expression in A549 cells. Collectively, these results suggest that EELP may exert an anti-cancer effect by cell cycle arrest at the G1 phase through both p53-dependent and p53-independent (ATM/CHK2/CDC25A/CDK2) pathways in A549 cells.

Extracellular acidity enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis via DR5 in gastric cancer cells

  • Hong, Ran;Han, Song Iy
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.5
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    • pp.513-523
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    • 2018
  • The tumor microenvironment greatly influences cancer cell characteristics, and acidic extracellular pH has been implicated as an essential factor in tumor malignancy and the induction of drug resistance. Here, we examined the characteristics of gastric carcinoma (GC) cells under conditions of extracellular acidity and attempted to identify a means of enhancing treatment efficacy. Acidic conditions caused several changes in GC cells adversely affecting chemotherapeutic treatment. Extracellular acidity did inhibit GC cell growth by inducing cell cycle arrest, but did not induce cell death at pH values down to 6.2, which was consistent with down-regulated cyclin D1 and up-regulated p21 mRNA expression. Additionally, an acidic environment altered the expression of atg5, HSPA1B, collagen XIII, collagen XXAI, slug, snail, and zeb1 genes which are related to regulation of cell resistance to cytotoxicity and malignancy, and as expected, resulted in increased resistance of cells to multiple chemotherapeutic drugs including etoposide, doxorubicin, daunorubicin, cisplatin, oxaliplatin and 5-FU. Interestingly, however, acidic environment dramatically sensitized GC cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Consistently, the acidity at pH 6.5 increased mRNA levels of DR4 and DR5 genes, and also elevated protein expression of both death receptors as detected by immunoblotting. Gene silencing analysis showed that of these two receptors, the major role in this effect was played by DR5. Therefore, these results suggest that extracellular acidity can sensitize TRAIL-mediated apoptosis at least partially via DR5 in GCs while it confers resistance to various type of chemotherapeutic drugs.

Stage specific transcriptome analysis of liver tissue from a crossbred Korean Native Pig (KNP × Yorkshire)

  • Kumar, Himansu;Srikanth, Krishnamoorthy;Park, Woncheol;Lee, Kyung-Tai;Choi, Bong-Hwan;Kim, Jun-Mo;Lim, Dajeong;Park, Jong-Eun
    • Journal of Biomedical and Translational Research
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    • v.19 no.4
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    • pp.116-124
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    • 2018
  • Korean Native Pig (KNP) has a uniform black coat color, excellent meat quality, white colored fat, solid fat structure and good marbling. However, its growth performance is low, while the western origin Yorkshire pig has high growth performance. To take advantage of the unique performance of the two pig breeds, we raised crossbreeds (KNP ${\times}$ Yorkshire to make use of the heterotic effect. We then analyzed the liver transcriptome as it plays an important role in fat metabolism. We sampled at two stages: 10 weeks and at 26 weeks. The stages were chosen to correspond to the change in feeding system. A total of 16 pigs (8 from each stage) were sampled and RNA sequencing was performed. The reads were mapped to the reference genome and differential expression analysis was performed with edgeR package. A total of 324 genes were found to be significantly differentially expressed (${\left|log2FC\right|}$ > 1 & q < 0.01), out of which 180 genes were up-regulated and 144 genes were down-regulated. Principal Component Analysis (PCA) showed that the samples clustered according to stages. Functional annotation of significant DEGs (differentially expressed genes) showed that GO terms such as DNA replication, cell division, protein phosphorylation, regulation of signal transduction by p53 class mediator, ribosome, focal adhesion, DNA helicase activity, protein kinase activity etc. were enriched. KEGG pathway analysis showed that the DEGs functioned in cell cycle, Ras signaling pathway, p53 signaling pathway, MAPK signaling pathway etc. Twenty-nine transcripts were also part of the DEGs, these were predominantly Cys2His2-like fold group (C2H2) family of zinc fingers. A protein-protein interaction (PPI) network analysis showed that there were three highly interconnected clusters, suggesting an enrichment of genes with similar biological function. This study presents the first report of liver tissue specific gene regulation in a cross-bred Korean pig.