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  1. Article ; Online: Triggered Polymersome Fusion.

    Fielden, Stephen D P / Derry, Matthew J / Miller, Alisha J / Topham, Paul D / O'Reilly, Rachel K

    Journal of the American Chemical Society

    2023  Volume 145, Issue 10, Page(s) 5824–5833

    Abstract: The contents of biological cells are retained within compartments formed of phospholipid membranes. The movement of material within and between cells is often mediated by the fusion of phospholipid membranes, which allows mixing of contents or excretion ... ...

    Abstract The contents of biological cells are retained within compartments formed of phospholipid membranes. The movement of material within and between cells is often mediated by the fusion of phospholipid membranes, which allows mixing of contents or excretion of material into the surrounding environment. Biological membrane fusion is a highly regulated process that is catalyzed by proteins and often triggered by cellular signaling. In contrast, the controlled fusion of polymer-based membranes is largely unexplored, despite the potential application of this process in nanomedicine, smart materials, and reagent trafficking. Here, we demonstrate triggered polymersome fusion. Out-of-equilibrium polymersomes were formed by ring-opening metathesis polymerization-induced self-assembly and persist until a specific chemical signal (pH change) triggers their fusion. Characterization of polymersomes was performed by a variety of techniques, including dynamic light scattering, dry-state/cryogenic-transmission electron microscopy, and small-angle X-ray scattering (SAXS). The fusion process was followed by time-resolved SAXS analysis. Developing elementary methods of communication between polymersomes, such as fusion, will prove essential for emulating life-like behaviors in synthetic nanotechnology.
    MeSH term(s) Scattering, Small Angle ; X-Ray Diffraction ; Polymers/chemistry ; Nanotechnology ; Microscopy, Electron, Transmission
    Chemical Substances Polymers
    Language English
    Publishing date 2023-03-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/jacs.2c13049
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  2. Article ; Online: Ablation of DGKα facilitates α-smooth muscle actin expression via the Smad and PKCδ signaling pathways during the acute phase of CCl

    Seino, Keiko / Nakano, Tomoyuki / Tanaka, Toshiaki / Hozumi, Yasukazu / Topham, Matthew K / Goto, Kaoru / Iseki, Ken

    FEBS open bio

    2023  Volume 14, Issue 2, Page(s) 300–308

    Abstract: Expression of α-smooth muscle actin (αSMA) is constitutive in vascular smooth muscle cells, but is induced in nonmuscle cells such as hepatic stellate cells (HSCs). HSCs play important roles in both physiological homeostasis and pathological response. ... ...

    Abstract Expression of α-smooth muscle actin (αSMA) is constitutive in vascular smooth muscle cells, but is induced in nonmuscle cells such as hepatic stellate cells (HSCs). HSCs play important roles in both physiological homeostasis and pathological response. HSC activation is characterized by αSMA expression, which is regulated by the TGFβ-induced Smad pathway. Recently, protein kinase C (PKC) was identified to regulate αSMA expression. Diacylglycerol kinase (DGK) metabolizes a second-messenger DG, thereby controlling components of DG-mediated signaling, such as PKC. In the present study we aimed to investigate the putative role of DGKα in αSMA expression. Use of a cellular model indicated that the DGK inhibitor R59949 promotes αSMA expression and PKCδ phosphorylation. It also facilitates Smad2 phosphorylation after 30 min of TGFβ stimulation. Furthermore, immunocytochemical analysis revealed that DGK inhibitor pretreatment without TGFβ stimulation engenders αSMA expression in a granular pattern, whereas DGK inhibitor pretreatment plus TGFβ stimulation significantly induces αSMA incorporation in stress fibers. Through animal model experiments, we observed that DGKα-knockout mice exhibit increased expression of αSMA in the liver after 48 h of carbon tetrachloride injection, together with enhanced phosphorylation levels of Smad2 and PKCδ. Together, these findings suggest that DGKα negatively regulates αSMA expression by acting on the Smad and PKCδ signaling pathways, which differentially regulate stress fiber incorporation and protein expression of αSMA, respectively.
    MeSH term(s) Animals ; Mice ; Actins/metabolism ; Liver/metabolism ; Muscle, Smooth/metabolism ; Signal Transduction ; Transforming Growth Factor beta ; Diacylglycerol Kinase
    Chemical Substances Actins ; Transforming Growth Factor beta ; Diacylglycerol Kinase (EC 2.7.1.107)
    Language English
    Publishing date 2023-12-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2651702-4
    ISSN 2211-5463 ; 2211-5463
    ISSN (online) 2211-5463
    ISSN 2211-5463
    DOI 10.1002/2211-5463.13749
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  3. Article ; Online: Mice lacking DGKε show increased beige adipogenesis in visceral white adipose tissue after long-term high fat diet in a COX-2- dependent manner.

    Nakano, Tomoyuki / Topham, Matthew K / Goto, Kaoru

    Advances in biological regulation

    2019  Volume 75, Page(s) 100659

    Abstract: Adipose tissue is a central site for energy storage in the form of triglyceride (TG). Under excess energy conditions, TG is synthesized by acylation of diacylglycerol (DG), whereas TG is broken down into DG and free fatty acid, which provide energy for ... ...

    Abstract Adipose tissue is a central site for energy storage in the form of triglyceride (TG). Under excess energy conditions, TG is synthesized by acylation of diacylglycerol (DG), whereas TG is broken down into DG and free fatty acid, which provide energy for mitochondrial lipid oxidation when needed. In this regard, DG is not merely an intermediate metabolite for TG metabolism; it also serves as a signaling molecule. DG kinase (DGK) phosphorylates DG to produce phosphatidic acid (PA). Consequently, DGK plays a pivotal role in the control of lipid metabolism and signal transduction pathway. Recently, a report has described that DGKε-knockout (KO) mice show expansion of epididymal white adipose tissue (WAT) together with the impairment of glucose clearance after short-term (40 days) high fat diet (HFD) feeding, an early presymptomatic phase of obesity in wild-type animals. Nevertheless, no report describes an investigation of their phenotype under long-term HFD feeding conditions. Remarkably, results obtained during long-term HFD feeding show that WAT mass is decreased significantly and that the blood glucose profile in response to glucose challenge is improved in DGKε-KO mice compared with wild-type, which contrast sharply against the phenotype shown for short-term HFD feeding. Morphological examination reveals that cyclooxygenase-2 (COX-2) expression and clusters of uncoupling protein 1 (UCP1)-positive multilocular brown-like ("beige") adipocyte are induced in DGKε-deficient WAT after long-term HFD feeding, suggesting that beige adipocytes facilitate energy expenditure during prolonged HFD feeding. Administration of celecoxib, a selective inhibitor of COX-2, abolishes the appearance of UCP1-positive beige adipocytes in DGKε-KO mice. These findings suggest that DGKε deficiency promotes visceral WAT remodeling in a COX-2-dependent manner under long-term HFD feeding conditions.
    MeSH term(s) Adipogenesis/drug effects ; Adipogenesis/genetics ; Adipose Tissue, Beige/enzymology ; Animals ; Cyclooxygenase 2/genetics ; Cyclooxygenase 2/metabolism ; Diacylglycerol Kinase/deficiency ; Diacylglycerol Kinase/metabolism ; Dietary Fats/pharmacology ; Intra-Abdominal Fat/enzymology ; Mice ; Mice, Knockout
    Chemical Substances Dietary Fats ; Ptgs2 protein, mouse (EC 1.14.99.-) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Diacylglycerol Kinase (EC 2.7.1.107)
    Language English
    Publishing date 2019-10-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2667413-0
    ISSN 2212-4934 ; 2212-4926
    ISSN (online) 2212-4934
    ISSN 2212-4926
    DOI 10.1016/j.jbior.2019.100659
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  4. Article ; Online: Downregulation of Diacylglycerol Kinase Delta Contributes to Hyperglycemia-Induced Insulin Resistance.

    Chibalin, Alexander V / Leng, Ying / Vieira, Elaine / Krook, Anna / Björnholm, Marie / Long, Yun Chau / Kotova, Olga / Zhong, Zhihui / Sakane, Fumio / Steiler, Tatiana / Nylén, Carolina / Wang, Jianjun / Laakso, Markku / Topham, Matthew K / Gilbert, Marc / Wallberg-Henriksson, Harriet / Zierath, Juleen R

    Cell

    2022  Volume 185, Issue 2, Page(s) 397–398

    Language English
    Publishing date 2022-01-21
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2021.12.044
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  5. Article: Signaling roles of diacylglycerol kinases.

    Topham, Matthew K

    Journal of cellular biochemistry

    2006  Volume 97, Issue 3, Page(s) 474–484

    Abstract: Diacylglycerol kinases (DGKs) attenuate diacylglycerol signaling by converting this lipid to phosphatidic acid (PA). The nine mammalian DGKs that have been identified are widely expressed, but each isoform has a unique tissue and subcellular distribution. ...

    Abstract Diacylglycerol kinases (DGKs) attenuate diacylglycerol signaling by converting this lipid to phosphatidic acid (PA). The nine mammalian DGKs that have been identified are widely expressed, but each isoform has a unique tissue and subcellular distribution. Their kinase activity is regulated by mechanisms that modify their access to diacylglycerol, directly affect their kinase activity, or alter their ability to bind to other proteins. In many cases, these enzymes regulate the activity of proteins that are modulated by either diacylglycerol or PA. Experiments using cultured cells and model organisms have demonstrated that DGKs have prominent roles in neuronal transmission, lymphocyte signaling, and carcinogenesis.
    MeSH term(s) Animals ; Diacylglycerol Kinase/metabolism ; Diglycerides/metabolism ; Humans ; Inositol Phosphates/metabolism ; Models, Biological ; Phosphatidic Acids/metabolism ; Signal Transduction
    Chemical Substances Diglycerides ; Inositol Phosphates ; Phosphatidic Acids ; Diacylglycerol Kinase (EC 2.7.1.107)
    Language English
    Publishing date 2006-02-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 392402-6
    ISSN 1097-4644 ; 0730-2312
    ISSN (online) 1097-4644
    ISSN 0730-2312
    DOI 10.1002/jcb.20704
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  6. Article ; Online: Deletion of diacylglycerol kinase ε confers susceptibility to obesity via reduced lipolytic activity in murine adipocytes.

    Nakano, Tomoyuki / Seino, Keiko / Wakabayashi, Ichiro / Stafforini, Diana M / Topham, Matthew K / Goto, Kaoru

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2018  Volume 32, Issue 8, Page(s) 4121–4131

    Abstract: ... Wakabayashi, I., Stafforini, D. M., Topham, M. K., Goto, K. Deletion of diacylglycerol kinase ε confers ... that its deficiency results in abnormal lipid metabolism such as obesity and insulin resistance.-Nakano, T., Seino, K ...

    Abstract Lipid metabolism is closely involved with signal transduction and energy homeostasis. Excess calorie intake causes abnormal lipid metabolism, promoting obesity and insulin resistance. Diacylglycerol (DG) represents not only a lipidic second messenger but also an intermediate metabolite for triglyceride metabolism in the endoplasmic reticulum (ER). However, it remains undetermined how the roles of DG in signaling and energy homeostasis is regulated within the cell. Of DG kinases (DGKs), which are enzymes that phosphorylate DG, DGKε resides in the ER. This study examined how DGKε is implicated in signal transduction and lipid homeostasis. DGKε-deficient mice were fed a high-fat diet (HFD) for 40 d. We observed that DGKε deficiency promotes fat accumulation in adipocytes and subsequently promotes insulin resistance in mice fed an HFD. This abnormal fat metabolism is mediated by down-regulation of lipolytic activities, such as adipose triglyceride lipase and hormone-sensitive lipase. In addition, activation of DG-sensitive PKC leads to insulin resistance in adipose tissue, which may be caused by delayed metabolism of DG. Our data suggest that DGKε links the second messenger signaling system to energy homeostasis in adipocytes and that its deficiency results in abnormal lipid metabolism such as obesity and insulin resistance.-Nakano, T., Seino, K., Wakabayashi, I., Stafforini, D. M., Topham, M. K., Goto, K. Deletion of diacylglycerol kinase ε confers susceptibility to obesity via reduced lipolytic activity in murine adipocytes.
    MeSH term(s) Adipocytes/metabolism ; Animals ; Diacylglycerol Kinase/metabolism ; Diet, High-Fat/adverse effects ; Down-Regulation/physiology ; Homeostasis/physiology ; Insulin Resistance/physiology ; Lipase/metabolism ; Lipid Metabolism/physiology ; Mice ; Obesity/metabolism ; Signal Transduction/physiology
    Chemical Substances Diacylglycerol Kinase (EC 2.7.1.107) ; Lipase (EC 3.1.1.3)
    Language English
    Publishing date 2018-03-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.201701050R
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  7. Article ; Online: Synthesis of core-shell polymer particles in supercritical carbon dioxide

    Kortsen, Kristoffer / Reynolds-Green, Morgan / Hopkins, Bradley / McLellan, Alison / Derry, Matthew J / Topham, Paul D / Titman, Jeremy J / Keddie, Daniel J / Taresco, Vincenzo / Howdle, Steven M

    Chemical communications (Cambridge, England)

    2023  Volume 59, Issue 98, Page(s) 14536–14539

    Abstract: A new, robust methodology for the synthesis of polystyrene-poly(methyl methacrylate) (PS-PMMA) core-shell particles using seeded dispersion polymerisation in supercritical carbon dioxide is reported, where the core-shell ratio can be controlled ... ...

    Abstract A new, robust methodology for the synthesis of polystyrene-poly(methyl methacrylate) (PS-PMMA) core-shell particles using seeded dispersion polymerisation in supercritical carbon dioxide is reported, where the core-shell ratio can be controlled predictably
    Language English
    Publishing date 2023-12-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 1472881-3
    ISSN 1364-548X ; 1359-7345 ; 0009-241X
    ISSN (online) 1364-548X
    ISSN 1359-7345 ; 0009-241X
    DOI 10.1039/d3cc04969h
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  8. Article: Mammalian diacylglycerol kinases: molecular interactions and biological functions of selected isoforms.

    Topham, Matthew K / Epand, Richard M

    Biochimica et biophysica acta

    2009  Volume 1790, Issue 6, Page(s) 416–424

    Abstract: The mammalian diacylglycerol kinases (DGK) are a group of enzymes having important roles in regulating many biological processes. Both the product and the substrate of these enzymes, i.e. diacylglycerol and phosphatidic acid, are important lipid ... ...

    Abstract The mammalian diacylglycerol kinases (DGK) are a group of enzymes having important roles in regulating many biological processes. Both the product and the substrate of these enzymes, i.e. diacylglycerol and phosphatidic acid, are important lipid signalling molecules. Each DGK isoform appears to have a distinct biological function as a consequence of its location in the cell and/or the proteins with which it associates. This review discusses three of the more extensively studied forms of this enzyme, DGKalpha, DGKvarepsilon, and DGKzeta. DGKalpha has an important role in immune function and its activity is modulated by several mechanisms. DGKvarepsilon has several unique features among which is its specificity for arachionoyl-containing substrates, suggesting its importance in phosphatidylinositol cycling. DGKzeta is expressed in many tissues and also has several mechanisms to regulate its functions. It is localized in several subcellular organelles, including the nucleus. The current state of our understanding of the properties and functions of these proteins is reviewed.
    MeSH term(s) Amino Acid Sequence ; Animals ; Diacylglycerol Kinase/chemistry ; Diacylglycerol Kinase/classification ; Diacylglycerol Kinase/genetics ; Diacylglycerol Kinase/metabolism ; Immune System/physiology ; Isoenzymes/chemistry ; Isoenzymes/classification ; Isoenzymes/genetics ; Isoenzymes/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Tertiary
    Chemical Substances Isoenzymes ; Diacylglycerol Kinase (EC 2.7.1.107)
    Language English
    Publishing date 2009-02-06
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbagen.2009.01.010
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  9. Article ; Online: Regulation of sonic hedgehog expression by integrin β1 and epidermal growth factor receptor in intestinal epithelium.

    Xu, Changxin / Li, Xiufen / Topham, Matthew K / Kuwada, Scott K

    IUBMB life

    2014  Volume 66, Issue 10, Page(s) 694–703

    Abstract: We previously found that conditional deletion of integrin β1 in intestinal epithelium of mice caused early postnatal lethality and intestinal phenotypic changes including excessive proliferation and defective differentiation of intestinal epithelium due ... ...

    Abstract We previously found that conditional deletion of integrin β1 in intestinal epithelium of mice caused early postnatal lethality and intestinal phenotypic changes including excessive proliferation and defective differentiation of intestinal epithelium due to loss of Hedgehog expression. Here, we link these defects to the Hedgehog (Hh) signaling pathway and show that loss of integrin β1 leads to excessive phosphorylation of MEK-1 and increased expression of ErbB receptors, including the epidermal growth factor receptor (EGFR). We show that increased EGFR signaling attenuates Hh abundance and that an EGFR inhibitor rescues conditional β1 integrin null pups from postnatal lethality. These studies link the loss of Hh expression in the intestinal epithelium of integrin β1-deficient mice to excessive EGFR/MAPK signaling, and identify a unique mechanism for crosstalk between stromal and epithelial signaling pathways that is critical for intestinal epithelial differentiation and function.
    MeSH term(s) Animals ; Blotting, Western ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; ErbB Receptors/genetics ; ErbB Receptors/metabolism ; Female ; Gene Expression Regulation ; Hedgehog Proteins/genetics ; Hedgehog Proteins/metabolism ; Immunoenzyme Techniques ; Integrases/metabolism ; Integrin beta1/physiology ; Intestinal Mucosa/cytology ; Intestinal Mucosa/metabolism ; Male ; Mice ; Mice, Knockout ; Microfilament Proteins/physiology ; RNA, Messenger/genetics ; Rats ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction
    Chemical Substances Hedgehog Proteins ; Integrin beta1 ; Microfilament Proteins ; RNA, Messenger ; Shh protein, mouse ; villin ; EGFR protein, mouse (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Cre recombinase (EC 2.7.7.-) ; Integrases (EC 2.7.7.-)
    Language English
    Publishing date 2014-10-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1492141-8
    ISSN 1521-6551 ; 1521-6543
    ISSN (online) 1521-6551
    ISSN 1521-6543
    DOI 10.1002/iub.1319
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  10. Article ; Online: Regulation and functions of diacylglycerol kinases.

    Shulga, Yulia V / Topham, Matthew K / Epand, Richard M

    Chemical reviews

    2011  Volume 111, Issue 10, Page(s) 6186–6208

    MeSH term(s) Alternative Splicing ; Animals ; Diacylglycerol Kinase/genetics ; Diacylglycerol Kinase/metabolism ; Subcellular Fractions/enzymology
    Chemical Substances Diacylglycerol Kinase (EC 2.7.1.107)
    Language English
    Publishing date 2011-10-12
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 207949-5
    ISSN 1520-6890 ; 0009-2665
    ISSN (online) 1520-6890
    ISSN 0009-2665
    DOI 10.1021/cr1004106
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