• Title/Summary/Keyword: catalytic factor

Search Result 156, Processing Time 0.027 seconds

Curcumin modulates the apolipoprotein B mRNA editing by coordinating the expression of cytidine deamination to uridine editosome components in primary mouse hepatocytes

  • He, Pan;Tian, Nan
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.23 no.3
    • /
    • pp.181-189
    • /
    • 2019
  • Curcumin, an active ingredient of Curcuma longa L., can reduce the concentration of low-density lipoproteins in plasma, in different ways. We had first reported that curcumin exhibits hypocholesterolemic properties by improving the apolipoprotein B (apoB) mRNA editing in primary rat hepatocytes. However, the role of curcumin in the regulation of apoB mRNA editing is not clear. Thus, we investigated the effect of curcumin on the expression of multiple editing components of apoB mRNA cytidine deamination to uridine (C-to-U) editosome. Our results demonstrated that treatment with $50{\mu}M$ curcumin markedly increased the amount of edited apoB mRNA in primary mouse hepatocytes from 5.13%-8.05% to 27.63%-35.61%, and significantly elevated the levels of the core components apoB editing catalytic polypeptide-1 (APOBEC-1), apobec-1 complementation factor (ACF), and RNA-binding-motif-protein-47 (RBM47), as well as suppressed the level of the inhibitory component glycine-arginine-tyrosine-rich RNA binding protein. Moreover, the increased apoB RNA editing by $50{\mu}M$ curcumin was significantly reduced by siRNA-mediated APOBEC-1, ACF, and RBM47 knockdown. These findings suggest that curcumin modulates apoB mRNA editing by coordinating the multiple editing components of the edito-some in primary hepatocytes. Our data provided evidence for curcumin to be used therapeutically to prevent atherosclerosis.

Evaluation of hydrogen recombination characteristics of a PAR using SPARC PAR experimental results

  • Jongtae Kim;Jaehoon Jung
    • Nuclear Engineering and Technology
    • /
    • v.55 no.12
    • /
    • pp.4382-4394
    • /
    • 2023
  • Passive auto-catalytic recombiners (PARs) are widely used to mitigate a hydrogen hazard. The first step to evaluate the hydrogen safety by PARs is to obtain qualified test data of the PARs for validation of their analytical model. SPARC PAR tests SP8 and SP9 were conducted to evaluate the hydrogen recombination characteristics of a honeycomb-shaped catalyst PAR. To obtain the hydrogen recombination rate from the PAR test data, two methods, Method-1 and Method-2, introduced by the THAI project, were applied. Since a large gradient of hydrogen concentration developed during hydrogen injection can cause a large error in the hydrogen mass obtained by integrating the measured hydrogen concentrations, a gate was installed at the PAR inlet to homogenize hydrogen in the test vessel before the PAR operation in the tests. A computational fluid dynamics (CFD) code with a PAR model was also applied to evaluate the characteristics of the PAR recombination according to the PAR inlet conditions, and the results were compared with those from Method-1 and Method-2. It was confirmed that the recombination rates from Method-1 require a correction factor to be compatible with results from Method-2 and the CFD simulation in the case of the SPARC-PAR tests.

Biological effects of zinc oxide nanoparticles on inflammation

  • Kim, Min-Ho
    • CELLMED
    • /
    • v.6 no.4
    • /
    • pp.23.1-23.6
    • /
    • 2016
  • With the rapid developments in nanotechnology, an increasing number of nanomaterials have been applied in various aspects of our lives. Recently, pharmaceutical nanotechnology with numerous advantages has growingly attracted the attention of many researchers. Zinc oxide nanoparticles (ZnO-NPs) are nanomaterials that are widely used in many fields including diagnostics, therapeutics, drug-delivery systems, electronics, cosmetics, sunscreens, coatings, ceramic products, paints, and food additives, due to their magnetic, catalytic, semiconducting, anti-cancer, anti-bacterial, anti-inflammatory, ultraviolet-protective, and binding properties. The present review focused on the recent research works concerning role of ZnO-NP on inflammation. Several studies have reported that ZnO-NP induces inflammatory reaction through the generation of reactive oxygen species by oxidative stress and production of inflammatory cytokines by activation of nuclear factor-${\kappa}B$ ($NF-{\kappa}B$). Meanwhile, other researchers reported that ZnO-NP exhibits an anti-inflammatory effect by inhibiting the up-regulation of inflammatory cytokines and the activation of $NF-{\kappa}B$, caspase-1, $I{\kappa}B$ $kinase{\beta}$, receptor interacting protein2, and extracellular signal-regulated kinase. Previous studies reported that size and shape of nanoparticles, surfactants used for nanoparticles protection, medium, and experimental conditions can also affect cellular signal pathway. This review indicated that the anti-inflammatory effectiveness of ZnO-NP was determined by the nanoparticle size as well as various experimental conditions. Therefore, the author suggests that pharmaceutical therapy with the ZnO-NP is one of the possible strategies to overcome the inflammatory reactions. However, further studies should be performed to maximize the anti-inflammatory effect of ZnO-NP to apply as a potential agent in biomedical applications.

Plasma Peptidome as a Source of Biomarkers for Diagnosis of Cholangiocarcinoma

  • Kotawong, Kanawut;Thitapakorn, Veerachai;Roytrakul, Sittiruk;Phaonakrop, Narumon;Viyanant, Vithoon;Na-Bangchang, Kesara
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.17 no.3
    • /
    • pp.1163-1168
    • /
    • 2016
  • Cholangiocarcinoma (CCA) is the bile duct cancer which constitutes one of the important public health problems in Thailand with high mortality rate, especially in the Opisthorchis viverrini (a parasite risk factor for CCA) endemic area of the northeastern region of the country. This study aimed to identify potential biomarkers from the plasma peptidome by CCA patients. Peptides were isolated using 10 kDa cut-off filter column and the flow-through was then used as a peptidome for LC-MS/MS analysis. A total of 209 peptides were obtained. Among these, 15 peptides were concerned with signaling pathways and 12 related to metabolic, regulatory, and biosynthesis of secondary metabolite pathways. Five exclusive peptides were identified as potential biomarkers, i.e. ETS domain-containing transcription factor ERF (P50548), KIAA0220 (Q92617), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 (P42338), LP2209 (Q6XYC0), and casein kinase II subunit alpha (P19784). Three of these biomarkers are signaling related molecules. A combination of these biomarkers for CCA diagnosis is proposed.

Structure and $Ca^{2+}$-ion effects on the function of $\alpha$-cyclodextrin Glucanotransferase from B. macerans : An X-ray study (Bacillus macerans에서 정제한 $\alpha$-cyclooextrin glucanotransferase의 구조와 칼슘이온이 기능에 미치는 영향 : X-ray 연구)

  • 최희욱;홍순강
    • KSBB Journal
    • /
    • v.19 no.2
    • /
    • pp.159-163
    • /
    • 2004
  • The X-ray structure of the cydodextrin-glucanotransferase of Bacillus macerans was solved by molecular replacement at 2.0 ${\AA}$ resolution. The refined structure has a crystallographic R-factor of 16.6%, (R$\sub$free/ = 20.5%). A new metal binding site occupied by two Ca$\^$2+/-ions was found at an accession channel of the active site. There is a large accumulation of negative charges that bind these Ca$\^$2+/-ions, thereby connecting segment ${\beta}$13-${\alpha}$G (residue 254-276) to the main body of domain A (at ${\alpha}$H, residue 283-297). The segment 313-${\alpha}$G contains the catalytic residue Glu258 between subsite 1 and -1 and Tyr260 (subsite 2) which is located at the entrance of the active site. The Ca$\^$2+/-site 3a,b may have a major role for the activity and specificity of this CGTase, although it is not even conserved for the a-subclass of CGTases.

Identification and Characterization of a Putative Basic Helix-Loop-Helix (bHLH) Transcription Factor Interacting with Calcineurin in C. elegans

  • Lee, Soo-Ung;Song, Hyun-Ok;Lee, Wonhae;Singaravelu, Gunasekaran;Yu, Jae-Ran;Park, Woo-Yoon
    • Molecules and Cells
    • /
    • v.28 no.5
    • /
    • pp.455-461
    • /
    • 2009
  • Calcineurin is a $Ca^{2+}$/Calmodulin activated Ser/Thr phosphatase that is well conserved from yeast to human. It is composed of catalytic subunit A (CnA) and regulatory subunit B (CnB). C. elegans homolog of CnA and CnB has been annotated to tax-6 and cnb-1, respectively and in vivo function of both genes has been intensively studied. In C. elegans, calcineurin play roles in various signaling pathways such as fertility, movement, body size regulation and serotonin-mediated egg laying. In order to understand additional signaling pathway(s) in which calcineurin functions, we screened for binding proteins of TAX-6 and found a novel binding protein, HLH-11. The HLH-11, a member of basic helix-loop-helix (bHLH) proteins, is a putative counterpart of human AP4 transcription factor. Previously bHLH transcription factors have been implicated to regulate many developmental processes such as cell proliferation and differentiation, sex determination and myogenesis. However, the in vivo function of hlh-11 is largely unknown. Here, we show that hlh-11 is expressed in pharynx, intestine, nerve cords, anal depressor and vuvla muscles where calcineurin is also expressed. Mutant analyses reveal that hlh-11 may have role(s) in regulating body size and reproduction. More interestingly, genetic epistasis suggests that hlh-11 may function to regulate serotoninmediated egg laying at the downstream of tax-6.

Suppression of Protein Kinase C and Nuclear Oncogene Expression as Possible Action Mechanisms of Cancer Chemoprevention by Curcumin

  • Lin, Jen-Kun
    • Archives of Pharmacal Research
    • /
    • v.27 no.7
    • /
    • pp.683-692
    • /
    • 2004
  • Curcumin (diferuloylmethane) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animal models. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase; and an effective inducer of heme oxygenase-1. Curcumin is also a potent inhibitor of protein kinase C(PKC), EGF(Epidermal growth factor)-receptor tyrosine kinase and LĸB kinase. Subsequently, curcumin inhibits the activation of NF(nucleor factor)KB and the expressions of oncogenes including c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction path-ways in the target cells. The oxidant tumor promoter TPA activates PKC by reacting with zinc thiolates present within the regulatory domain, while the oxidized form of cancer chemopreventive agent such as curcumin can inactivate PKC by oxidizing the vicinal thiols present within the catalytic domain. Recent studies indicated that proteasome-mediated degradation of cell proteins playa pivotal role in the regulation of several basic cellular processes including differentiation, proliferation, cell cycling, and apoptosis. It has been demonstrated that curcumin-induced apoptosis is mediated through the impairment of ubiquitin-proteasome pathway. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are the major metabolites of curcumin in mice, rats and humans.

Zearalenone regulates key factors of the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1-nuclear factor erythroid 2-related factor 2 signaling pathway in duodenum of post-weaning gilts

  • Cheng, Qun;Jiang, Shu zhen;Huang, Li bo;Yang, Wei ren;Yang, Zai bin
    • Animal Bioscience
    • /
    • v.34 no.8
    • /
    • pp.1403-1414
    • /
    • 2021
  • Objective: This study explored the mechanism of the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway under conditions of zearalenone (ZEA)-induced oxidative stress in the duodenum of post-weaning gilts. Methods: Forty post-weaning gilts were randomly allocated to four groups and fed diets supplemented with 0, 0.5, 1.0, or 1.5 mg/kg ZEA. Results: The results showed significant reductions in the activity of the antioxidant enzymes total superoxide dismutase and glutathione peroxidase and increases the malondialdehyde content with increasing concentrations of dietary ZEA. Immunohistochemical analysis supported these findings by showing a significantly increased expression of Nrf2 and glutathione peroxidase 1 (GPX1) with increasing concentrations of ZEA. The relative mRNA and protein expression of Nrf2, GPX1 increased linearly (p<0.05) and quadratically (p<0.05), which was consistent with the immunohistochemical results. The relative mRNA expression of Keap1 decreased linearly (p<0.05) and quadratically (p<0.05) in the duodenum as the ZEA concentration increased in the diet. The relative mRNA expression of modifier subunit of glutamate-cysteine ligase (GCLM) increased quadratically (p<0.05) in all ZEA treatment groups and the relative mRNA expression of quinone oxidoreductase 1 (NQO1) catalytic subunit of glutamate-cysteine ligase decreased linearly (p<0.05) and quadratically (p<0.05) in the ZEA1.0 group and ZEA1.5 group. The relative protein expression of Keap1 and GCLM decreased quadratically (p<0.05) in the duodenum as the ZEA concentration increased in the diet, respectively. The relative protein expression of NQO1 increased linearly (p<0.05) and quadratically (p<0.05) in all ZEA treatment groups in the duodenum. Conclusion: These findings suggest that ZEA regulates the expression of key factors of the Keap1-Nrf2 signaling pathway in the duodenum, which enables resistance to ZEA-induced oxidative stress. Further studies are needed to examine the effects of ZEA induced oxidative stress on other tissues and organs in post-weaning gilts.

Mutational Analysis Elucidates the Role of Conserved 237 Arginine in 23S rRNA Methylation, Which is in the Concave Cleft Region of ErmSF (ErmSF에서 두 도메인 사이에 존재하는 잘 보존된 237번 아르지닌 잔기의 위치 지정 치환 변이의 효소 활성 검색을 통한 역할 규명)

  • Jin, Hyung Jong
    • Korean Journal of Microbiology
    • /
    • v.49 no.2
    • /
    • pp.105-111
    • /
    • 2013
  • The Erm family of adenine-$N^6$ methyltransferases (MTases) is responsible for the development of resistance to macrolide-lincosamide-streptogramin B antibiotics through the methylation of 23S ribosomal RNA. Recently, it has been proposed that well conserved amino acids in ErnC' located in concave cleft between N-terminal 'catalytic' domain and C-terminal 'RNA-binding' domain interacts with substrate RNA. We carried out the site-directed mutagenesis and studied the function of the ErmSF R237 mutant in vitro and in vivo. R237 amino acid residue is located in the concave cleft between two domains. Furthermore this residue is very highly conserved in almost all the Erm family. Purified mutant protein exhibited only 51% enzyme activity compared to wild-type. Escherichia coli with R237A mutant protein compared to the wild-type protein expressing E. coli did not show any difference in its MIC (minimal inhibitory concentration) suggesting that even with lowered enzyme activity, mutant protein was able to efficiently methylate 23S rRNA to confer the resistance on E. coli expressing this protein. But this observation strongly suggests that R237 of ErmSF probably interacts with substrate RNA affecting enzyme activity significantly.

Degradation of a nano-thick Au/Pt bilayered catalytic layer with an electrolyte in dye sensitized solar cells (염료감응태양전지의 Au/Pt 이중 촉매층의 전해질과의 반응에 따른 열화)

  • Noh, Yunyoung;Song, Ohsung
    • Journal of the Korea Academia-Industrial cooperation Society
    • /
    • v.15 no.6
    • /
    • pp.4013-4018
    • /
    • 2014
  • A 0.45 $cm^2$ DSSC device with a glass/FTO/blocking layer/$TiO_2$/N719(dye)/electrolyte/50 nm-Pt/50 nm-Au/FTO/glass was prepared to examine the stability of the Au/Pt bilayered counter electrode (CE) with electrolyte and the energy conversion efficiency (ECE) of dye-sensitized solar cells (DSSCs). For comparison, a 100 nm-thick Pt only CE DSSC was also prepared using the same method. The photovoltaic properties, such as the short circuit current density ($J_{sc}$), open circuit voltage ($V_{oc}$), fill factor (FF), and ECE, were checked using a solar simulator and potentiostat with time after assembling the DSSC. The microstructure of the Au/Pt bilayer was examined by optical microscopy after 0~25 minutes. The ECE of the Pt only CE-employed DSSC was 4.60 %, which did not show time dependence. On the other hand, for the Au/Pt CE DSSC, the ECEs after 0, 5 and 15 minutes were 5.28 %, 3.64 % and 2.09 %, respectively. The corrosion areas of the Au/Pt CE determined by optical microscopy after 0, 5, and 25 minutes were 0, 21.92 and 34.06 %. These results confirmed that the ECE and catalytic activity of Au/Pt CE decreased drastically with time. Therefore, a Au/Pt CE-employed DSSC may be superior to the Pt only CE-employed one immediately after integration of the device, but it would degrade drastically with time.