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51.
Summary The activity of two enzymes of the UDP-glucose and UDP-galactose biosynthetic pathway—phosphoglucose-isomerase and phosphoglucomutase—have been followed during morphogenesis of the unicellular green alga Acetabularia mediterranea. We have found that the increase in enzyme activities during morphogenesis represents de novo synthesis. The kinetic constants (K
m, K
i) of phosphoglucose-isomerase are similar to those found for the enzyme from rabbit muscle; mannose-6-phosphate was found to be a competitive inhibitor.The increase in activity of phosphoglucose-isomerase parallels the linear increase in total protein, neither showing changes with cap formation. In contrast, the activity of phosphoglucomutase is enhanced markedly when cap formation starts.Whether the nucleus is present or absent does not affect the above mentioned properties of the two enzymes. From this fact we conclude that the enzyme syntheses are regulated by the cytoplasm, probably at the level of translation. Contributions of DNA from chloroplasts and mitochondria can be excluded because in anucleate cells, which have an already established gradient of m-RNA, actinomycin D (10 g/ml) has no effect on the synthesis of these enzymes.There are also differences in the spatial distribution of the two enzymes. We were able to show that both enzymes are synthesized unequally in different regions of the cells.
Abkürzungen PGI Phosphoglucose-isomerase - PGM Phosphoglucomutase - UDPG-Pyr UDPG-Pyrophosphorylase - G-6-PDH Glucose-6-phosphat Dehydrogenase - G-6-P Glucose-6-phosphat - F-6-P Fructose-6-phosphat - G-1-P Glucose-1-phosphat - UDPG Uridin-diphosphat-glucose - G-1,6-diP Glucose-1,6-diphosphat - 6-PG 6-Phosphogluconat - TRAP Triäthanolamin-Puffer - K m Michaelis-Konstante - K p veränderte K m - K i Inhibitor-Konstante 相似文献
Abkürzungen PGI Phosphoglucose-isomerase - PGM Phosphoglucomutase - UDPG-Pyr UDPG-Pyrophosphorylase - G-6-PDH Glucose-6-phosphat Dehydrogenase - G-6-P Glucose-6-phosphat - F-6-P Fructose-6-phosphat - G-1-P Glucose-1-phosphat - UDPG Uridin-diphosphat-glucose - G-1,6-diP Glucose-1,6-diphosphat - 6-PG 6-Phosphogluconat - TRAP Triäthanolamin-Puffer - K m Michaelis-Konstante - K p veränderte K m - K i Inhibitor-Konstante 相似文献
52.
Mechanical forces are an important contributor to cell fate specification and cell migration during embryonic development in animals. Similarities between embryogenesis and regeneration, particularly with regards to pattern formation and large-scale tissue movements, suggest similarly important roles for physical forces during regeneration. While the influence of the mechanical environment on stem cell differentiation in vitro is being actively exploited in the fields of tissue engineering and regenerative medicine, comparatively little is known about the role of stresses and strains acting during animal regeneration. In this review, we summarize published work on the role of physical principles and mechanical forces in animal regeneration. Novel experimental techniques aimed at addressing the role of mechanics in embryogenesis have greatly enhanced our understanding at scales from the subcellular to the macroscopic – we believe the time is ripe for the field of regeneration to similarly leverage the tools of the mechanobiological research community. 相似文献
53.
Lena Hoffmann Marcel S. Waclawczyk Stephan Tang Eva-Maria Hanschmann Manuela Gellert Marco B. Rust Carsten Culmsee 《Cell death & disease》2021,12(11)
Many cell death pathways, including apoptosis, regulated necrosis, and ferroptosis, are relevant for neuronal cell death and share common mechanisms such as the formation of reactive oxygen species (ROS) and mitochondrial damage. Here, we present the role of the actin-regulating protein cofilin1 in regulating mitochondrial pathways in oxidative neuronal death. Cofilin1 deletion in neuronal HT22 cells exerted increased mitochondrial resilience, assessed by quantification of mitochondrial ROS production, mitochondrial membrane potential, and ATP levels. Further, cofilin1-deficient cells met their energy demand through enhanced glycolysis, whereas control cells were metabolically impaired when challenged by ferroptosis. Further, cofilin1 was confirmed as a key player in glutamate-mediated excitotoxicity and associated mitochondrial damage in primary cortical neurons. Using isolated mitochondria and recombinant cofilin1, we provide a further link to toxicity-related mitochondrial impairment mediated by oxidized cofilin1. Our data revealed that the detrimental impact of cofilin1 on mitochondria depends on the oxidation of cysteine residues at positions 139 and 147. Overall, our findings show that cofilin1 acts as a redox sensor in oxidative cell death pathways of ferroptosis, and also promotes glutamate excitotoxicity. Protective effects by cofilin1 inhibition are particularly attributed to preserved mitochondrial integrity and function. Thus, interfering with the oxidation and pathological activation of cofilin1 may offer an effective therapeutic strategy in neurodegenerative diseases.Subject terms: Apoptosis, Cell death in the nervous system, Neurodegeneration 相似文献
54.
Christian Maercker Stefan Stoll Katja Rosenkranz Eva-Maria Becker Hans J. Lipps 《Genesis (New York, N.Y. : 2000)》1997,21(3):201-211
A repetitive element from the hypotrichous ciliate Stylonychia lemnae was characterized by restriction and hybridization analysis. This repetitive element is present in about 5,000–7,000 copies per haploid genome in the micronucleus and the macronuclear anlagen. Its DNA sequence is very conserved, but the length of the repetitive sequence blocs is variable. In some cases, it is associated with telomeric sequences and macronucleus–homologous sequences. Restriction analysis of genomic micronuclear and macronuclear anlagen DNA and in situ hybridization showed that the repetitive sequences are amplified during the formation of polytene chromosomes. They are localized in many bands of the polytene chromosomes and are eliminated during the degradation of the polytene chromosomes. Possible functions of the repetitive sequences during macronuclear differentiation are discussed. Dev. Genet. 21:201–211, 1997.© 1997 Wiley-Liss, Inc. 相似文献
55.
Michela Baccini Eva-Maria Bachmaier Annibale Biggeri Mark V. Boekschoten Freek G. Bouwman Lorraine Brennan Robert Caesar Saverio Cinti Susan L. Coort Katie Crosley Hannelore Daniel Christian A. Drevon Susan Duthie Lars Eijssen Ruan M. Elliott Marjan van Erk Chris Evelo Mike Gibney Carolin Heim Graham W. Horgan Ian T. Johnson Thomas Kelder Robert Kleemann Teake Kooistra Martijn P. van Iersel Edwin C. Mariman Claus Mayer Gerard McLoughlin Michael Müller Francis Mulholland Ben van Ommen Abigael C. Polley Estelle Pujos-Guillot Isabel Rubio-Aliaga Helen M. Roche Baukje de Roos Manuela Sailer Giulia Tonini Lynda M. Williams Nicole de Wit 《Genes & nutrition》2008,3(3-4):147-151
56.
Link AJ Skretas G Strauch EM Chari NS Georgiou G 《Protein science : a publication of the Protein Society》2008,17(10):1857-1863
G protein-coupled receptors (GPCRs) are notoriously difficult to express, particularly in microbial systems. Using GPCR fusions with the green fluorescent protein (GFP), we conducted studies to identify bacterial host effector genes that result in a general and significant enhancement in the amount of membrane-integrated human GPCRs that can be produced in Escherichia coli. We show that coexpression of the membrane-bound AAA+ protease FtsH greatly enhances the expression yield of four different class I GPCRs, irrespective of the presence of GFP. Using this new expression system, we produced 0.5 and 2 mg/L of detergent-solubilized and purified full-length central cannabinoid receptor (CB1) and bradykinin receptor 2 (BR2) in shake flask cultures, respectively, two proteins that had previously eluded expression in microbial systems. 相似文献
57.
Fabian Klaus Eva-Maria Gehring Agathe Zürn Joerg Laufer Ricco Lindner Nathalie Strutz-Seebohm Jeremy M. Tavaré Jeffrey D. Rothstein Christoph Boehmer Monica Palmada Ivonne Gruner Undine E. Lang Guiscard Seebohm Florian Lang 《Neurochemistry international》2009,54(5-6):372-377
The Na+,glutamate cotransporter EAAT3 is expressed in a wide variety of tissues. It accomplishes transepithelial transport and the cellular uptake of acidic amino acids. Regulation of EAAT3 activity involves a signaling cascade including the phosphatidylinositol-3 (PI3)-kinase, the phosphoinositide dependent kinase PDK1, and the serum and glucocorticoid inducible kinase SGK1. Targets of SGK1 include the mammalian phosphatidylinositol-3-phosphate-5-kinase PIKfyve (PIP5K3). The present experiments explored whether PIKfyve participates in the regulation of EAAT3 activity. To this end, EAAT3 was expressed in Xenopus oocytes with or without SGK1 and/or PIKfyve and glutamate-induced current (Iglu) determined by dual electrode voltage clamp. In Xenopus oocytes expressing EAAT3 but not in water injected oocytes glutamate induced an inwardly directed Iglu. Coexpression of either, SGK1 or PIKfyve, significantly enhanced Iglu in EAAT3 expressing oocytes. The increased Iglu was paralleled by increased EAAT3 protein abundance in the oocyte cell membrane. Iglu and EAAT3 protein abundance were significantly larger in oocytes coexpressing EAAT3, SGK1 and PIKfyve than in oocytes expressing EAAT3 and either, SGK1 or PIKfyve, alone. Coexpression of the inactive SGK1 mutant K127NSGK1 did not significantly alter Iglu in EAAT3 expressing oocytes and completely reversed the stimulating effect of PIKfyve coexpression on Iglu. The stimulating effect of PIKfyve on Iglu was abolished by replacement of the serine by alanine in the SGK consensus sequence (S318APIKfyve). Moreover, additional coexpression of S318APIKfyve significantly blunted Iglu in Xenopus oocytes coexpressing SGK1 and EAAT3. The observations demonstrate that PIKfyve participates in EAAT3 regulation likely downstream of SGK1. 相似文献
58.
Andreas Koeberle Eva-Maria Haberl Antonietta Rossi Carlo Pergola Friederike Dehm Hinnak Northoff Reinhard Troschuetz Lidia Sautebin Oliver Werz 《Bioorganic & medicinal chemistry》2009,17(23):7924-7932
Selective inhibition of pro-inflammatory prostaglandin (PG)E2 formation via microsomal PGE2 synthase-1 (mPGES-1) might be superior over inhibition of all cyclooxygenase (COX)-derived products by non-steroidal anti-inflammatory drugs (NSAIDs) and coxibs. We recently showed that benzo[g]indol-3-carboxylates potently suppress leukotriene biosynthesis by inhibiting 5-lipoxygenase. Here, we describe the discovery of benzo[g]indol-3-carboxylates as a novel class of potent mPGES-1 inhibitors (IC50 ? 0.1 μM). Ethyl 2-(3-chlorobenzyl)-5-hydroxy-1H-benzo[g]indole-3-carboxylate (compound 7a) inhibits human mPGES-1 in a cell-free assay (IC50 = 0.6 μM) as well as in intact A549 cells (IC50 = 2 μM), and suppressed PGE2 pleural levels in rat carrageenan-induced pleurisy. Inhibition of cellular COX-1/2 activity was significantly less pronounced. Compound 7a significantly reduced inflammatory reactions in the carrageenan-induced mouse paw edema and rat pleurisy. Together, based on the select and potent inhibition of mPGES-1 and 5-lipoxygenase, benzo[g]indol-3-carboxylates possess potential as novel anti-inflammatory drugs with a valuable pharmacological profile. 相似文献
59.
Maria Laura Aon-Bertolino Juan Ignacio Romero Pablo Galeano Mariana Holubiec Maria Sol Badorrey Gustavo Ezequiel Saraceno Eva-Maria Hanschmann Christopher Horst Lillig Francisco Capani 《Biochimica et Biophysica Acta (BBA)/General Subjects》2011
Background
The oxidoreductases of the thioredoxin (Trx) family of proteins play a major role in the cellular response to oxidative stress. Redox imbalance is a major feature of brain damage. For instance, neuronal damage and glial reaction induced by a hypoxic–ischemic episode is highly related to glutamate excitotoxicity, oxidative stress and mitochondrial dysfunction. Most animal models of hypoxia–ischemia in the central nervous system (CNS) use rats to study the mechanisms involved in neuronal cell death, however, no comprehensive study on the localization of the redox proteins in the rat CNS was available.Methods
The aim of this work was to study the distribution of the following proteins of the thioredoxin and glutathione/glutaredoxin (Grx) systems in the rat CNS by immunohistochemistry: Trx1, Trx2, TrxR1, TrxR2, Txnip, Grx1, Grx2, Grx3, Grx5, and γ-GCS, peroxiredoxin 1 (Prx1), Prx2, Prx3, Prx4, Prx5, and Prx6. We have focused on areas most sensitive to a hypoxia–ischemic insult: Cerebellum, striatum, hippocampus, spinal cord, substantia nigra, cortex and retina.Results and conclusions
Previous studies implied that these redox proteins may be distributed in most cell types and regions of the CNS. Here, we have observed several remarkable differences in both abundance and regional distribution that point to a complex interplay and crosstalk between the proteins of this family.General significance
We think that these data might be helpful to reveal new insights into the role of thiol redox pathways in the pathogenesis of hypoxia–ischemia insults and other disorders of the CNS.This article is part of a Special Issue entitled Human and Murine Redox Protein Atlases. 相似文献60.
Höhne M Lorscheider J von Bardeleben A Dufner M Scharf MA Gödel M Helmstädter M Schurek EM Zank S Gerke P Kurschat C Sivritas SH Neumann-Haefelin E Huber TB Reinhardt HC Schauss AC Schermer B Fischbach KF Benzing T 《Molecular and cellular biology》2011,31(16):3241-3251
Neph proteins are evolutionarily conserved membrane proteins of the immunoglobulin superfamily that control the formation of specific intercellular contacts. Cell recognition through these proteins is essential in diverse cellular contexts such as patterning of the compound eye in Drosophila melanogaster, neuronal connectivity in Caenorhabditis elegans, and the formation of the kidney filtration barrier in mammals. Here we identify the PDZ and BAR domain protein PICK1 (protein interacting with C-kinase 1) as a Neph-interacting protein. Binding required dimerization of PICK1, was dependent on PDZ domain protein interactions, and mediated stabilization of Neph1 at the plasma membrane. Moreover, protein kinase C (PKCα) activity facilitated the interaction through releasing Neph proteins from their binding to the multidomain scaffolding protein zonula occludens 1 (ZO-1), another PDZ domain protein. In Drosophila, the Neph homologue Roughest is essential for sorting of interommatidial precursor cells and patterning of the compound eye. RNA interference-mediated knockdown of PICK1 in the Drosophila eye imaginal disc caused a Roughest destabilization at the plasma membrane and a phenotype that resembled rst mutation. These data indicate that Neph proteins and PICK1 synergistically regulate cell recognition and contact formation. 相似文献