• Title/Summary/Keyword: degradation pathway

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Studies on Gene Expression of Yukmijihwang-tang using High-throughput Gene Expression Analysis Techniques (대규모 유전자 분석 기법을 이용한 육미지황원의 유전자 발현 연구)

  • Kang, Bong-Joo;Kim, Yun-Taik;Cho, Dong-Wuk
    • Korean Journal of Oriental Medicine
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    • v.8 no.2 s.9
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    • pp.95-107
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    • 2002
  • Yukmijihwang-tang(YM) is a noted herbal prescription in Chinese and Korean traditional medicines, and it has been known to reinforce the vital essence and has been widely used for a variety of disease such as stroke, osteoporosis, anti-tumor, and hypothyrodism. Regarding its traditional use, YM has been known to reinforce the Yin (vital essence) of liver and kidney. Also it has been known to reinforce nutrition and biological function in brain. Recently, studies suggested that YM increase antioxidant activities and exert the protective effect against oxidant-induced liver cell injury. We investigated the high-throughput gene expression analysis on the Yukmijihwang-tang administrated in SD rats. Microarray data were validated on a limited number of genes by semiquantitative RT-PCR and Western blot analyses. The recent availability of microarrays provides an attractive strategy for elaborating an unbiased molecular profile of large number of genes in drug discovery This experimental approach offers the potential to identify molecules or cellular pathways not previously associated with herbal medicine. Total RNA from normal control brain and Yukmijihwang-tang administrated brain were hybridized to microarrays containing 10,000 rat genes. The 52 genes were found to be up-regulated(twice or more) excluding EST gene. The nine genes were found to be down-regulated(twice or more) excluding EST gene. Gene array technology was used to identify for the first time many genes expression pathway analysis that arecell cycle pathway, apoptosis pathway, electron transport chain pathway, cytoplasmic ribosomal protein pathway, fatty acid degradation pathway, and TGF-beta signaling pathway. These differentially expressed genes pathway analysis have not previously been iavestigated in the context of herbal medicine efficacy and represent novel factors for further study of the mechanism of herbal medicine efficacy.

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Catabolic Degradation of 4-Chlorobiphenyl by Pseudomonas sp. DJ-12 via Consecutive Reaction of meta-Cleavage and Hydrolytic Dechlorination

  • Chae, Jong-Chan;Kim, Eunheui;Park, Sang-Ho;Kim, Chi-Kyung
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.5 no.6
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    • pp.449-455
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    • 2000
  • Pseudomonas sp. strain DJ-12 is a bacterial isolate capable of degrading 4-chlorobiphenyl (4CBP) as a carbon and energy source. The catabolic degradation of 4CBP by the strain DJ-12 was studied along with the genetic organization of the genes responsible for the crucial steps of the catabolic degradation. The catabolic pathway was characterized as being conducted by consecutive reactions of the meta-cleavage of 4CBP, hydrolytic dechlorination of 4-chlorobenzoate (4CBA), hydroxylation of 4-hydroxybenzoate, and meta-cleavage of protocatechuate. The pcbC gene responsible for the meta-cleavage of 4CBP only showed a 30 to 40% homology in its deduced amino acid sequence compared to those of the corresponding genes from other strains. The amino acid sequence of 4CBA-CoA dechlorinase showed an 86% homology with that of Pseudomonas sp. CBS3, yet only a 50% homology with that of Arthrobacter spp. However, the fcb genes for the hydrolytic dechlorination of 4CBA in Pseudomonas sp. DJ-12 showed an uniquely different organization from those of CBS3 and other reported strains. Accordingly, these results indicate that strain DJ-12 can degrade 4CBA completely via meta-cleavage and hydrolytic dechlorination using enzymes that are uniquely different in their amino acid sequences from those of other bacterial strains with the same degradation activities.

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NDRG3-mediated lactate signaling in hypoxia

  • Park, Kyung Chan;Lee, Dong Chul;Yeom, Young Il
    • BMB Reports
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    • v.48 no.6
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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]

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

  • 김현영;송홍규
    • Korean Journal of Microbiology
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    • v.38 no.4
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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.

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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    • v.38 no.4
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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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Mechanisms of amino acid sensing in mTOR signaling pathway

  • Kim, Eun-Jung
    • Nutrition Research and Practice
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    • v.3 no.1
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    • pp.64-71
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    • 2009
  • Amino acids are fundamental nutrients for protein synthesis and cell growth (increase in cell size). Recently, many compelling evidences have shown that the level of amino acids is sensed by extra- or intra-cellular amino acids sensor(s) and regulates protein synthesis/degradation. Mammalian target of rapamycin complex 1 (mTORC1) is placed in a central position in cell growth regulation and dysregulation of mTOR signaling pathway has been implicated in many serious human diseases including cancer, diabetes, and tissue hypertrophy. Although amino acids are the most potent activator of mTORC1, how amino acids activate mTOR signaling pathway is still largely unknown. This is partly because of the diversity of amino acids themselves including structure and metabolism. In this review, current proposed amino acid sensing mechanisms to regulate mTORC1 and the evidences pro/against the proposed models are discussed.

Eriodictyol Inhibits the Production and Gene Expression of MUC5AC Mucin via the IκBα-NF-κB p65 Signaling Pathway in Airway Epithelial Cells

  • Yun, Chawon;Lee, Hyun Jae;Lee, Choong Jae
    • Biomolecules & Therapeutics
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    • v.29 no.6
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    • pp.637-642
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    • 2021
  • In this study, we investigated whether eriodictyol exerts an effect on the production and gene expression of MUC5AC mucin in human pulmonary epithelial NCI-H292 cells. The cells were pretreated with eriodictyol for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. The effect of eriodictyol on PMA-induced nuclear factor kappa B (NF-κB) signaling pathway was also investigated. Eriodictyol suppressed the MUC5AC mucin production and gene expression induced by PMA via suppression of inhibitory kappa Bα degradation and NF-κB p65 nuclear translocation. These results suggest that eriodictyol inhibits mucin gene expression and production in human airway epithelial cells via regulation of the NF-κB signaling pathway.

Regulation of adductor muscle growth by the IGF-1/AKT pathway in the triploid Pacific oyster, Crassostrea gigas

  • Kim, Eun-Young;Choi, Youn Hee
    • Fisheries and Aquatic Sciences
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    • v.22 no.9
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    • pp.19.1-19.10
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    • 2019
  • We investigated the insulin-like growth factor 1 (IGF-1)/AKT signaling pathway involved in muscle formation, growth, and movement in the adductor muscle of triploid Pacific oyster, Crassostrea gigas. Large and small triploid oysters (LTs and STs) cultured under identical conditions were screened, and the signaling pathways of individuals with superior growth were compared and analyzed. mRNA and protein expression levels of actin, troponin, tropomyosin, and myosin, proteins important in muscle formation, were higher in LTs compared with STs. Expression levels of IGF-1, IGF binding protein (IGFBP), and IGFBP complex acid-labile subunit were also higher in LTs compared with STs. Phosphorylation of the IGF receptor as well as that of AKT was high in LTs. In addition, the expression of phosphomammalian target of rapamycin and phospho-glycogen synthase kinase $3{\beta}$ was increased and the expression of Forkhead box O3 was decreased in LTs. Therefore, we suggested that the IGF-1/AKT signaling pathway affects the formation, growth, and movement of the adductor muscle in triploid oysters.

Regulation of the Gene Expression of Airway MUC5AC Mucin through NF-κB Signaling Pathway by Artesunate, an Antimalarial Agent

  • Kyung-il Kim;Rajib Hossain;Jiho Ryu;Hyun Jae Lee;Choong Jae Lee
    • Biomolecules & Therapeutics
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    • v.31 no.5
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    • pp.544-549
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    • 2023
  • In this study, artesunate, an antimalarial agent, was investigated for its potential effect on the gene expression of airway MUC5AC mucin. The human pulmonary epithelial NCI-H292 cells were pretreated with artesunate for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of artesunate on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also examined. Artesunate inhibited the glycoprotein production and mRNA expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest artesunate suppresses the gene expression of mucin through regulation of NF-kB signaling pathway, in human pulmonary epithelial cells.

Amino-terminal arginylation as a degradation signal for selective autophagy

  • Cha-Molstad, Hyunjoo;Kwon, Yong Tae;Kim, Bo Yeon
    • BMB Reports
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    • v.48 no.9
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    • pp.487-488
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    • 2015
  • The ubiquitin-proteasome system and the autophagy lysosome system are the two major protein degradation machineries in eukaryotic cells. These two systems coordinate the removal of unwanted intracellular materials, but the mechanism by which they achieve this synchronization is largely unknown. The ubiquitination of substrates serves as a universal degradation signal for both systems. Our study revealed that the amino-terminal Arg, a canonical N-degron in the ubiquitin-proteasome system, also acts as a degradation signal in autophagy. We showed that many ER residents, such as BiP, contain evolutionally conserved arginylation permissive pro-N-degrons, and that certain inducers like dsDNA or proteasome inhibitors cause their translocation into the cytoplasm where they bind misfolded proteins and undergo amino-terminal arginylation by arginyl transferase 1 (ATE1). The amino-terminal Arg of BiP binds p62, which triggers p62 oligomerization and enhances p62-LC3 interaction, thereby stimulating autophagic delivery and degradation of misfolded proteins, promoting cell survival. This study reveals a novel ubiquitin-independent mechanism for the selective autophagy pathway, and provides an insight into how these two major protein degradation pathways communicate in cells to dispose the unwanted proteins. [BMB Reports 2015; 48(9): 487-488]