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Biochemical Journal

Chris Nevitt, John G Tooley, Christine E Schaner Tooley
Deciphering the histone code has illustrated that acetylation or methylation on the same residue can have analogous or opposing roles. However, little is known about the interplay between these post-translational modifications (PTMs) on the same non-histone residues. We have recently discovered that N-terminal acetyltransferases (NATs) and N-terminal methyltransferases (NRMTs) can have overlapping substrates and identified myosin regulatory light chain 9 (MYL9) as the first confirmed protein to occur in either a-amino-methylated (Nα-methyl) or a-amino-acetylated (Nα-acetyl) states in vivo Here we aim to determine if these PTMs function similarly or create different MYL9 proteoforms with distinct roles...
September 21, 2018: Biochemical Journal
Werner E G Müller, Maximilian Ackermann, Emad Tolba, Meik Neufurth, Ivan Ivetac, Maria Kokkinopoulou, Heinz C Schröder, Xiaohong Wang
The in vitro tube formation assay with human umbilical vein endothelial cells (HUVEC) was applied to identify the extra- and intracellular sources of metabolic energy/ATP required for cell migration during the initial stage of microvascularization. Extracellularly, the physiological energy-rich polymer, inorganic polyphosphate [polyP], applied as biomimetic amorphous calcium polyP microparticles [Ca-polyP-MP], is functioning as a substrate for ATP generation most likely via the action of the alkaline phosphatase [ALP] and the adenylate kinase [AK] T he linear Ca-polyP-MP with a size of 40 phosphate units, close to the physiological polyP in the blood platelets , were found to increase endothelial cell tube formation, as well as the intracellular ATP levels...
September 21, 2018: Biochemical Journal
Olga Vitavska, Rabea Bartölke, Katharina Tabke, Jürgen J Heinisch, Helmut Wieczorek
The solute carrier 45 family (SLC45) was defined in the course of the Human Genome Project and consists of four members, A1 - A4, which show only 20-30% identity of amino acid sequences among each other. All these members exhibit an identity of approximately 20% to plant H+ /sucrose cotransporters. Recently, we expressed members of the murine SLC45 family in yeast cells and demonstrated that they are, like their plant counterparts, H+ /sucrose cotransporters. In contrast to the plant proteins, SLC45 transporters recognise also the monosaccharides glucose and fructose as physiological substrates and seem to be involved in alternative sugar supply as well as in osmoregulation of several mammalian tissues...
September 20, 2018: Biochemical Journal
Esraa Saadi, Sharon Tal, Liza Barki-Harrington
Catalysis of arachidonic acid (AA) by cyclooxygenase-2 (COX-2) gives rise to a single product that serves as a precursor for all prostaglandins, which are central mediators of inflammation. Rapid upregulation of COX-2 expression in response to pro-inflammatory stimuli is a well-characterized means of generating the large pool of prostaglandins necessary for inflammation. However, an efficient inflammatory process must also terminate rapidly and thus requires cessation of COX-2 enzymatic activity and removal of excess protein from the cell...
September 14, 2018: Biochemical Journal
Ofek Oren, Victor Banerjee, Ran Taube, Niv Papo
Aggregation and accumulation of the 42-residue amyloid β peptide (Aβ42) in the extracellular matrix and within neuronal cells is considered a major cause of neuronal cell cytotoxicity and death in Alzheimer's disease (AD) patients. Therefore, molecules that bind to Aβ42 and prevent its aggregation are therapeutically promising as AD treatment. Here, we show that a non-self-aggregating Aβ42 variant carrying two surface mutations, F19S and L34P (Aβ42DM ), inhibits wild type Aβ42 aggregation and significantly reduces Aβ42-mediated cell cytotoxicity...
September 13, 2018: Biochemical Journal
Reema Kathuria, Anish Kumar Mondal, Rohan Sharma, Samarjit Bhattacharyya, Kausik Chattopadhyay
Vibrio cholerae cytolysin (VCC) is a ß-barrel pore-forming toxin with potent membrane-damaging cell-killing activity. Previous studies employing the model membranes of lipid vesicles (liposomes) have shown that pore formation by VCC requires presence of cholesterol in the liposome membranes. However, exact role of cholesterol in the mode of action of VCC still remains unclear. Most importantly, implication of cholesterol, if any, in regulating the pore-formation mechanism of VCC in the biomembranes of eukaryotic cells remains unexplored...
September 11, 2018: Biochemical Journal
Laëtitia Gorisse, Zhigang Li, Andrew C Hedman, David B Sacks
Axl is a tyrosine kinase receptor that is important for hematopoiesis, the innate immune response, platelet aggregation, engulfment of apoptotic cells and cell survival. Binding of growth arrest-specific protein 6 (Gas6) activates Axl signaling, but the mechanism of inactivation of the Axl receptor is poorly understood. In this study, we show that IQGAP1 modulates Axl signaling. IQGAP1 is a scaffold protein that integrates cell signaling pathways by binding several growth factor receptors and intracellular signaling molecules...
September 5, 2018: Biochemical Journal
Cecilia Chavarría, Sebastián Rodriguez-Bottero, Celia Quijano, Patricia Cassina, José M Souza
Synucleinopathies are a group of neurodegenerative disorders characterized by the presence of aggregated and fibrillar forms of α-synuclein (α-syn). Herein we analyse the effect of different species of α-syn including monomeric, oligomeric, and fibrillar forms of the protein, on rat astrocytes. Astrocytes treated with these distinct forms of α-syn showed an increase in long and thin processes and glial fibrillary acidic protein expression, indicating cell activation; high levels of intracellular oxidants and increased expression of cytokines...
September 5, 2018: Biochemical Journal
Michael G Friedrich, Zhen Wang, Kevin L Schey, Roger J W Truscott
The breakdown of long-lived proteins is associated with aging, as well as disease, however our understanding of the molecular processes involved is still limited. Of particular relevance, crosslinked proteins are often reported in aged tissues but the mechanisms for their formation are poorly understood. In this study, sites of protein crosslinking in human ocular lenses were characterized using proteomic techniques. In long-lived lens proteins, several sites of crosslinking were found to involve the addition of Lys to Asp or Asn residues...
September 4, 2018: Biochemical Journal
Ravi Prakash Sanyal, Amol Samant, Vishal Prashar, Hari Sharan Misra, Ajay Saini
Superoxide dismutases (SODs, EC belong to an important group of antioxidant metalloenzymes. Multiple SODs exist for scavenging of reactive oxygen species (ROS) in different cellular compartments to maintain an intricate ROS balance. The present study deals with molecular and biochemical characterization of CuZn SOD encoded by LOC_Os03g11960 (referred to as OsCSD3), which is the least studied among the four rice isozymes. The OsCSD3 showed higher similarity to peroxisomal SODs in plants. The OsCSD3 transcript was up-regulated in response to salinity, drought and oxidative stress...
September 4, 2018: Biochemical Journal
Meha Shikhi, Deepak T Nair, Dinakar M Salunke
Proteins belonging to cupin superfamily are known to have critical and diverse physiological functions. However, 7S globulins family, which is also a part of cupin superfamily were undermined as only seed storage proteins. Structure determination of native protein - Vic_CAPAN from Capsicum annuum was carried out, and its physiological functions were explored after purifying the protein by ammonium sulfate precipitation followed by size exclusion chromatography. The crystal structure of vicilin determined at 2...
September 4, 2018: Biochemical Journal
Elaine C Thomas, Sharon C Hook, Alexander Gray, Alexandra Chadt, David Carling, Hadi Al-Hasani, Kate J Heesom, D Grahame Hardie, Jeremy M Tavaré
AMP-activated protein kinase (AMPK) is a key regulator of cellular and systemic energy homeostasis which achieves this through the phosphorylation of a myriad of downstream targets. One target is TBC1D1 a Rab-GTPase-Activating Protein (GAP) that regulates glucose uptake in muscle cells by integrating insulin signalling with that promoted by muscle contraction. Ser237 in TBC1D1 is a target for phosphorylation by AMPK, an event which may be important in regulating glucose uptake. Here we show AMPK heterotrimers containing the α1, but not the α2, isoform of the catalytic subunit forms an unusual and stable association with TBC1D1, but not its paralogue AS160...
August 22, 2018: Biochemical Journal
Ann Maria Kruse Hansen, Sara Gry Vienberg, Kirsten Lykkegaard, Xin Zhao, Goa Tingqing, Dan Han, Xujia Zhang, Henning Thøgersen, Kristian Sass-Ørum, Tina Møller Tagmose, Kirsten Raun, Birgitte Andersen
Fibroblast growth factors (FGF) 19, 21 and 23 are characterized by being endocrinely secreted and require co-receptor α- or β-klotho (BKL) for binding and activation of the FGF receptors (FGFR). FGF15 is the rodent orthologue of human FGF19 but the two proteins share only 52% amino acid identity. Despite the physiological role of FGF21 and FGF19 being quite different, both lower blood glucose (BG) when administered to diabetic mice. The present study was designed to clarify why two human proteins with distinct physiological function both lower blood glucose in db/db mice and if the mouse orthologue FGF15 has similar effect to FGF19 and FGF21...
August 20, 2018: Biochemical Journal
Muhammad Aaqil Khan, Muhammad Hamayun, Amjad Iqbal, Sumera Afzal Khan, Anwar Hussain, Sajjad Asaf, Abdul Latif Khan, Byung Wook Yun, In-Jung Lee
Flooding is an abiotic stress that creates hypoxic conditions triggered by redox potential leading to restricted growth and grain yield in plants. In the current study, we have investigated the effect of exogenous gibberellins (GA4+7 ) on soybean under flooding stress. A regulatory role of GAs on biochemical changes in soybean plants (including, chlorophyll contents, endogenous bioactive GA1 and GA4 , endogenous jasmonic acid and abscisic acid) has been elucidated after 3 and 6 h of flooding stress. The modulation of stress related bio-chemicals and their genetic determinants [for instance abscisic acid (ABA; Timing of CAB expression1 - TOC1, ABA-receptor - ABAR ) and NO ( S -nitrosoglutathione reductase- GSNOR1 , NO overproducer1- NOX and nitrite reductase- NR )] in response to short term flooding stress were also explored...
August 20, 2018: Biochemical Journal
Bea Unterer, Veit Wiesmann, Mekala Gunasekaran, Heinrich Sticht, Clara Tenkerian, Jürgen Behrens, Maria Leone, Felix B Engel, Nathalie Britzen-Laurent, Elisabeth Naschberger, Thomas Wittenberg, Michael Stürzl
Interferon-gamma (IFN‑γ) is a pleiotropic cytokine that exerts important functions in inflammation, infectious diseases and cancer. The large GTPase human guanylate-binding protein 1 (GBP‑1) is among the most strongly IFN‑γ-induced cellular proteins. Previously it has been shown that GBP-1 mediates manifold cellular responses to IFN‑γ including the inhibition of proliferation, spreading, migration, and invasion and through this exerts anti-tumorigenic activity. However, the mechanisms of GBP-1 anti-tumorigenic activities remain poorly understood...
August 17, 2018: Biochemical Journal
Blanca E Ruiz-Medina, Denisse A Cadena-Medina, Edmundo Esparza, Amy J Arrieta, Robert A Kirken
Regulation of intracellular signaling pathways in lymphocytes is critical for cell homeostasis and immune response. Interleukin 2 (IL-2), a key regulator of lymphocytes, signals following receptor-ligand engagement and subsequent recruitment and activation of effector proteins including JAKs and STATs. Lymphocytes can also be regulated by the central nervous system through the β2 adrenergic receptor (β2AR) pathway which can affect cell trafficking, proliferation, differentiation, and cytokine production. The crosstalk between these two signaling pathways represents an important mechanism that has yet to be fully elucidated...
August 17, 2018: Biochemical Journal
Pierre-Andre Barbeau, Paula M Miotto, Graham P Holloway
The mechanisms regulating oxidative phosphorylation during exercise remain poorly defined, however key mitochondrial proteins, including carnitine-palmitoyl transferase-I (CPT-I) and adenine-nucleotide translocase have redox sensitive sites. Interestingly muscle contraction has recently been shown to increase mitochondrial membrane potential and reactive oxygen species (ROS) production, therefore we aimed to determine if mitochondrial derived ROS influences bioenergetic responses to exercise. Specifically, we examined the influence of acute exercise on mitochondrial bioenergetics in WT and transgenic mice (MCAT) possessing attenuated mitochondrial ROS...
August 15, 2018: Biochemical Journal
Tomás M Fernandes, Leonor Morgado, Carlos A Salgueiro
The Geobacter metallireducens bacterium can couple the oxidation of a wide range of compounds to the reduction of several extracellular electron acceptors, including pollutants or electrode surfaces for current production in microbial fuel cells. For these reasons, G. metallireducens are of interest for practical biotechnological applications. The use of such electron acceptors relies on a mechanism that permits electrons to be transferred to the cell exterior. The cytochrome PpcA from G. metallireducens is a member of a family composed by five periplasmic triheme cytochromes, which are important to bridge the electron transfer from the cytoplasmic donors to the extracellular acceptors...
August 2, 2018: Biochemical Journal
Jo Ann Janovick, Timothy P Spicer, Thomas D Bannister, Emery Smith, Vadivel Ganapathy, Louis Scampavia
A series of compounds formerly identified by high throughput screening was studied for their ability to serve as pharmacoperones for the Vasopressin Type 2 Receptor (V2R) mutant L83Q that is known to cause nephrogenic diabetes insipidus (NDI).  Three compounds were particularly effective in re-routing the mutant receptor in a concentration-dependent manner, were neither agonists nor antagonists, and displayed low cellular toxicity. Compound 1 was most effective and can be used as a molecular probe for future studies of how small molecules may impact NDI caused by mutant V2R...
August 1, 2018: Biochemical Journal
Satoshi Murakami, Kumiko Kondo, Shinya Katayama, Satoshi Hara, Ei-Ichiro Sunamura, Eiki Yamashita, Georg Groth, Toru Hisabori
F1 -ATPase forms the membrane-associated segment of Fo F1 -ATP synthase - the fundamental enzyme complex in cellular bioenergetics for ATP hydrolysis and synthesis. Here, we report a crystal structure of the central F1 subcomplex, consisting of the rotary shaft γ subunit and the inhibitory ε subunit, from the photosynthetic cyanobacterium Thermosynechococcus elongatus BP-1, at 1.98 Å resolution. In contrast to their homologous bacterial and mitochondrial counterparts, the γ subunits of photosynthetic organisms harbour a unique insertion of 35-40 amino acids...
July 27, 2018: Biochemical Journal
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