• 제목/요약/키워드: Molecular pathway

검색결과 1,754건 처리시간 0.03초

Monoterpenoid Loliolide Regulates Hair Follicle Inductivity of Human Dermal Papilla Cells by Activating the AKT/β-Catenin Signaling Pathway

  • Lee, Yu Rim;Bae, Seunghee;Kim, Ji Yea;Lee, Junwoo;Cho, Dae-Hyun;Kim, Hee-Sik;An, In-Sook;An, Sungkwan
    • Journal of Microbiology and Biotechnology
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    • 제29권11호
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    • pp.1830-1840
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    • 2019
  • Loliolide is one of the most ubiquitous monoterpenoid compounds found in algae, and its potential therapeutic effect on various dermatological conditions via agent-induced biological functions, including anti-oxidative and anti-apoptotic properties, was demonstrated. Here, we investigated the effects of loliolide on hair growth in dermal papilla (DP) cells, the main components regulating hair growth and loss conditions. For this purpose, we used a three-dimensional (3D) DP spheroid model that mimics the in vivo hair follicle system. Biochemical assays showed that low doses of loliolide increased the viability and size of 3D DP spheroids in a dose-dependent manner. This result correlated with increases in expression levels of hair growth-related autocrine factors including VEGF, IGF-1, and KGF. Immunoblotting and luciferase-reporter assays further revealed that loliolide induced AKT phosphorylation, and this effect led to stabilization of β-catenin, which plays a crucial role in the hair-inductive properties of DP cells. Further experiments showed that loliolide increased the expression levels of the DP signature genes, ALP, BMP2, VCAN, and HEY1. Furthermore, conditioned media from loliolide-treated DP spheroids significantly enhanced proliferation and the expression of hair growth regulatory genes in keratinocytes. These results suggested that loliolide could function in the hair growth inductivity of DP cells via the AKT/β-catenin signaling pathway.

NDRG3-mediated lactate signaling in hypoxia

  • Park, Kyung Chan;Lee, Dong Chul;Yeom, Young Il
    • BMB Reports
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    • 제48권6호
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    • pp.301-302
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    • 2015
  • Hypoxia is associated with many pathological conditions as well as the normal physiology of metazoans. We identified a lactate-dependent signaling pathway in hypoxia, mediated by the oxygen- and lactate-regulated protein NDRG family member 3 (NDRG3). Oxygen negatively regulates NDRG3 expression at the protein level via the PHD2/VHL system, whereas lactate, produced in excess under prolonged hypoxia, blocks its proteasomal degradation by binding to NDRG3. We also found that the stabilized NDRG3 protein promotes angiogenesis and cell growth under hypoxia by activating the Raf-ERK pathway. Inhibiting cellular lactate production abolishes NDRG3-mediated hypoxia responses. The NDRG3-Raf-ERK axis therefore provides the genetic basis for lactate-induced hypoxia signaling, which can be exploited for the development of therapies targeting hypoxia-induced diseases in addition to advancing our understanding of the normal physiology of hypoxia responses. [BMB Reports 2015; 48(6): 301-302]

PMA Activates Stat3 in the Jak/Stat Pathway and Induces SOCS5 in Rat Brain Astrocytes

  • Hwang, Mi-Na;Kim, Kwang Soo;Choi, Yo-Woo;Jou, Ilo;Yoon, Sungpil
    • Molecules and Cells
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    • 제23권1호
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    • pp.94-99
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    • 2007
  • Suppressors of cytokine signaling (SOCS) family members are negative feedback regulators of the Jak/Stat pathway, which is an essential inflammatory signaling pathway. We investigated expression of eight members of the SOCS family in rat astrocytes, using two inflammatory stimulants, PMA and IFN-${\gamma}$. Only a few SOCS genes were induced by both stimulants, and we detected an increase in SOCS5 protein with PMA. PMA activated the Jnk, Erk, p38, and Jak/Stat signal pathways. In addition, it increased the level of activated-Stat3 resulting from tyrosine phosphorylation. A gel-shift assay showed that a protein in nuclear extracts from PMA-treated cells was able to bind to Stat binding elements. These results suggest that activated Stat3 binds to SOCS promoters and leads to their transcriptional induction.

Hippo Signaling Circuit and Divergent Tissue Growth in Mammalian Eye

  • Moon, Kyeong Hwan;Kim, Jin Woo
    • Molecules and Cells
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    • 제41권4호
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    • pp.257-263
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    • 2018
  • Vertebrate organ development is accompanied by demarcation of tissue compartments, which grow coordinately with their neighbors. Hence, perturbing the coordinative growth of neighboring tissue compartments frequently results in organ malformation. The growth of tissue compartments is regulated by multiple intercellular and intracellular signaling pathways, including the Hippo signaling pathway that limits the growth of various organs. In the optic neuroepithelial continuum, which is partitioned into the retina, retinal pigment epithelium (RPE) and ciliary margin (CM) during eye development, the Hippo signaling activity operates differentially, as it does in many tissues. In this review, we summarize recent studies that have explored the relationship between the Hippo signaling pathway and growth of optic neuroepithelial compartments. We will focus particularly on the roles of a tumor suppressor, neurofibromin 2 (NF2), whose expression is not only dependent on compartment-specific transcription factors, but is also subject to regulation by a Hippo-Yap feedback signaling circuit.

Degradation of Polyvinyl Alcohol by Brevibacillus laterosporus: metabolic Pathway of Polyvinyl Alcohol to Acetate

  • Lim, Joong-Gyu;Park, Doo-Hyun
    • Journal of Microbiology and Biotechnology
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    • 제11권6호
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    • pp.928-933
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    • 2001
  • Approximately 0.1 mg/ml of polyvinyl alcohol (PVA) was degraded by the growing cell, Brevibacillus laterospours, for 30 h, and 0.2 mg/ml of PVA was degraded by the cell-free extract that was isolated from Brevibacillus laterosporus. Approximately $0.29{\mu}g$/ml of acetic acid was produced from PVA by using the cell-free extract as a catalyst for 40 min. $V_{max}\;and\;K_m$ value of purified PAV-degradation enzyme was 3.75g/l and 2.75 g/l/min in reaction with EDTA and 3.99 g/l and 2.98 g/l/min in reaction without EDTA, respectively. Molecular weight of the purified enzyme determined by SDS-PAGE was 63,000 Da. Alcohol dehydrogenase and aldehyde dehydrogenase activities were qualitatively detected on a native acrylamide gel by an active staining method, indicating the existence of the metabolic pathway to use PVA as a substrate.

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An integrated bioinformatics analysis of mouse testis protein profiles with new understanding

  • Liu, Fujun;Wang, Haiyan;Li, Jianyuan
    • BMB Reports
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    • 제44권5호
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    • pp.347-351
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    • 2011
  • The testis is major male gonad responsible for spermatogenesis and steroidogenesis. Much knowledge is still remained to be learned about the control of these events. In this study, we performed a comprehensive bioinformatics analysis on 1,196 mouse testis proteins screened from public protein database. Integrated function and pathway analysis were performed through Database for Annotation, Visualization and Integrated Discovery (DAVID) and ingenuity Pathway Analysis (IPA), and significant features were clustered. Protein membrane organization and gene density on chromosomes were analyzed and discussed. The enriched bioinformatics analysis could provide clues and basis to the development of diagnostic markers and therapeutic targets for infertility and male contraception.

Simultaneous Utilization of Two Different Pathways in Degradation of 2,4,6-Trinitrotoluene by White Rot Fungus Irpex lacteus

  • 김현영;송홍규
    • 미생물학회지
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    • 제38권4호
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    • pp.250-250
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    • 2002
  • This study confirmed that white rot fungus Irpex lacteus was able to metabolize 2,4,6-trinitrotoluene (TNT) with two different initial transformations. In one metabolic pathway of TNT a nitro group was removed from the aromatic ring of TNT. Hydride-Meisenheimer complexes of TNT (H/sup -/-TNT), colored dark redo were confirmed as the intermediate in this transformation by comparison with the synthetic compounds. 2,4-Dinitrotoluene as a following metabolic product was detected, and nitrite produced by denitration of $H^-$-TNT supported this transformation. In the other TNT pathway, nitro groups in TNT were successively reduced to amino groups via hydroxylamines. Hydroxylamino-dinitrotoluenes and amino-dinitrotoluenes were identified as the intermediates. The activity of a membrane-associated aromatic nitroreductase was detected in the cell-free extract of I. lacteus. This enzyme catalyzed the nitro group reduction of TNT with NADPH as a cofactor, Enzyme activity was not observed in the presence of molecular oxygen.

Estimation of Theoretical Yield for Ethanol Production from D-Xylose by Recombinant Saccharomyces cerevisiae Using Metabolic Pathway Synthesis Algorithm

  • Lee, Tae-Hee;Kim, Min-Young;Ryu, Yeon-Woo;Seo, Jin-Ho
    • Journal of Microbiology and Biotechnology
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    • 제11권3호
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    • pp.384-388
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    • 2001
  • The metabolic pathway synthesis algorithm was applied to estimate the maximum ethanol yield from xylose in a model recombinant Saccharomyces cerevisiae strain containing the genes involved in xylose metabolism. The stoichiometrically independent pathways were identified by constructing a biochemical reaction network for conversion of xylose to ethanol in the recombinant S. cerevisiae. Two independent pathways were obtained in xylose-assimilating recombinant S. cerevisiae as opposed to six independent pathways for conversion of glucose to ethanol. The maximum ethanol yield from xylose was estimated to be 0.46 g/g, which was lower than the known value of 0.51 g/g for glucose-fermenting and wild-type xylose-fermenting yeasts.

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Simultaneous Utilization of Two Different Pathways in Degradation of 2,4,6-Trinitrotoluene by White Rot Fungus Irpex lacteus

  • Kim, Hyoun-Young;Song, Hong-Gyu
    • Journal of Microbiology
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    • 제38권4호
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    • pp.250-254
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    • 2000
  • This study confirmed that white rot fungus Irpex lacteus was able to metabolize 2,4,6-trinitrotoluene (TNT) with two different initial transformations. In one metabolic pathway of TNT a nitro group was removed from the aromatic ring of TNT. Hydride-Meisenheimer complexes of TNT (H$\^$-/-TNT), colored dark redo were confirmed as the intermediate in this transformation by comparison with the synthetic compounds. 2,4-Dinitrotoluene as a following metabolic product was detected, and nitrite produced by denitration of H$\^$-/-TNT supported this transformation. In the other TNT pathway, nitro groups in TNT were successively reduced to amino groups via hydroxylamines. Hydroxylamino-dinitrotoluenes and amino-dinitrotoluenes were identified as the intermediates. The activity of a membrane-associated aromatic nitroreductase was detected in the cell-free extract of I. lacteus. This enzyme catalyzed the nitro group reduction of TNT with NADPH as a cofactor, Enzyme activity was not observed in the presence of molecular oxygen.

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Gene Expression Profiling of Human Bronchial Epithelial (BEAS-2B) Cells Treated with Nitrofurantoin, a Pulmonary Toxicant

  • Kim, Youn-Jung;Song, Mee;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • 제3권4호
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    • pp.222-230
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    • 2007
  • Some drugs may be limited in their clinical application due to their propensity towards their adverse effects. Toxicogenomic technology represents a useful approach for evaluating the toxic properties of new drug candidates early in the drug discovery process. Nitrofurantoin (NF) is clinical chemotherapeutic agent and antimicrobial and used to treatment of urinary tract infections. However, NF has been shown to result in pulmonary toxic effects. In this research, we revealed the changing expression gene profiles in BEAS-2B, human bronchial epithelial cell line, exposed to NF by using human oligonucleotide chip. Through the clustering analysis of gene expression profiles, we identified 136 up-regulated genes and 379 down-regulated genes changed by more than 2-fold by NF. This study identifies several interesting targets and functions in relation to NF-induced toxicity through a gene ontology analysis method including biological process, cellular components, molecular function and KEGG pathway.