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    3479 results match your criteria Biological chemistry[Journal]

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    Transcytosis of payloads that are noncovalently complexed to bispecific antibodies across the hCMEC/D3 blood-brain-barrier model.
    Biol Chem 2017 Dec 20. Epub 2017 Dec 20.
    1Roche Pharma Research and Early Development (pRED), Therapeutic Modalities - Large Molecule Research, Roche Innovation Center Munich, D-82377 Penzberg, Germany.
    A transcellular shuttle system was generated for delivery of non-covalently linked payloads across blood-brain-barrier (BBB) endothelial cells. Transcytosis enabling shuttles are composed of bispecific antibodies (bsAbs) that simultaneously bind transferrin receptor (TfR) and haptens such as digoxigenin or biocytinamide. Haptenylated payloads are attached to these vehicles via non-covalent hapten-antibody complexation. Read More

    The effect of lncRNA HOTAIR on chemoresistance of ovarian cancer through regulation of HOXA7.
    Biol Chem 2018 Feb 19. Epub 2018 Feb 19.
    Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, No. 32 Yihuan Road, Chengdu 610072, Sichuan, China.
    This study aimed at investigating the biological functions of long non-coding RNAs (lncRNAs) hox transcript antisense intergenic RNA (HOTAIR) in resistant ovarian cancer cells, exploring the regulation effect of HOTAIR on HOXA7, and investigating their influence on the chemosensitivity of ovarian cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for the verification of HOTAIR expression in resistant and sensitive groups. How HOTAIR downregulation affected cell proliferation, migration and invasion, and apoptosis were determined using the MTT assay and the colony formation assay, the Transwell assay and flow cytometry analysis, respectively. Read More

    The AGO proteins: an overview.
    Biol Chem 2017 Nov 27. Epub 2017 Nov 27.
    1Department of Biotechnology, University of Kashmir, Srinagar 190006, J&K, India.
    Small RNAs govern almost every biological process in eukaryotes associating with the Argonaute proteins to form the RNA-induced silencing complex (mRISC). Argonaute proteins constitute the core of RISCs with different members having variety of protein binding partners and biochemical properties. This review focuses on the AGO subfamily of the Argonautes that are ubiquitously expressed and are associated with small RNAs. Read More

    Evidence that cell surface localization of serine protease activity facilitates cleavage of the protease activated receptor CDCP1.
    Biol Chem 2017 Nov 27. Epub 2017 Nov 27.
    1Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Qld 4102, Australia.
    The cellular receptor CUB Domain Containing Protein 1 (CDCP1) is commonly elevated and functionally important in a range of cancers. CDCP1 is cleaved by serine proteases at adjacent sites, arginine 368 (R368) and lysine 369 (K369), which induces cell migration in vitro, and metastasis in vivo. We demonstrate that membrane localization of serine protease activity increases efficacy of cleavage of CDCP1, and that both secreted and membrane anchored serine proteases can have distinct preferences for cleaving at CDCP1-R368 and -K369. Read More

    Structural changes at the myrtenol backbone reverse its positive allosteric potential into inhibitory GABAA receptor modulation.
    Biol Chem 2018 Feb 21. Epub 2018 Feb 21.
    Institute for Clinical Neurobiology, Julius-Maximilians-Universität Würzburg, Versbacherstr. 5, D-97078 Würzburg, Germany.
    GABAA receptors are ligand-gated anion channels that form pentameric arrangements of various subunits. Positive allosteric modulators of GABAA receptors have been reported as being isolated either from plants or synthesized analogs of known GABAA receptor targeting drugs. Recently, we identified monoterpenes, e. Read More

    Determination of selenium during pathogenesis of hepatic fibrosis employing hydride generation and inductively coupled plasma mass spectrometry.
    Biol Chem 2018 Feb 19. Epub 2018 Feb 19.
    Department of Hepatology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan.
    Serum and liver selenium levels were studied during the pathogenesis of N-nitrosodimethylamine (NDMA) induced hepatic fibrosis in rats. The degree of fibrosis was assessed with Masson's trichrome staining and quantifying collagen content in the liver. Lipid peroxides were measured in blood and liver samples and total glutathione and glutathione peroxidase were assayed in the liver tissue to evaluate oxidative stress. Read More

    Update on mitochondria and muscle aging: all wrong roads lead to sarcopenia.
    Biol Chem 2018 Feb 19. Epub 2018 Feb 19.
    Department of Geriatrics, Neuroscience and Orthopedics, Teaching Hospital "Agostino Gemelli", Catholic University of the Sacred Heart School of Medicine, L.go F. Vito 1, I-00168 Rome, Italy.
    Sarcopenia is a well-known geriatric syndrome that has been endorsed over the years as a biomarker allowing for the discrimination, at a clinical level, of biological from chronological age. Multiple candidate mechanisms have been linked to muscle degeneration during sarcopenia. Among them, there is wide consensus on the central role played by the loss of mitochondrial integrity in myocytes, secondary to dysfunctional quality control mechanisms. Read More

    CRISPR/Cas9-mediated modification of the extreme C-terminus impairs PDGF-stimulated activity of Duox2.
    Biol Chem 2018 Feb 22. Epub 2018 Feb 22.
    M.V. Lomonosov Moscow State University Medical Center, Lomonosovsky ave, 27-10, Moscow 119991, Russia.
    Duox2 belongs to the large family of NADPH-oxidase enzymes that are implicated in immune response, vasoregulation, hormone synthesis, cell growth and differentiation via the regulated synthesis of H2O2 and reactive oxygen species. We and others have shown that Duox2 and H2O2 are involved in platelet-derived growth factor (PDGF) induced migration of fibroblasts. Now, using the CRISPR/Cas9-mediated genome editing we demonstrate that the extreme C-terminal region of Duox2 is required for PDGF-stimulated activity of Duox2 and H2O2 production. Read More

    In vitro reconstitution and biochemical characterization of human phospholipid scramblase 3: phospholipid specificity and metal ion binding studies.
    Biol Chem 2017 Jun 27. Epub 2017 Jun 27.
    2Sathyanarayana N. Applied and Industrial Microbiology Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600 036, India.
    Human phospholipid scramblase 3 (hPLSCR3) is a single pass transmembrane protein that plays a vital role in fat metabolism, mitochondrial function, structure, maintenance and apoptosis. The mechanism of action of scramblases remains still unknown and the role of scramblases in phospholipid translocation is heavily debated. hPLSCR3 is the only member of scramblase family localized to mitochondria and is involved in cardiolipin translocation at the mitochondrial membrane. Read More

    Generation of superoxide and hydrogen peroxide by side reactions of mitochondrial 2-oxoacid dehydrogenase complexes in isolation and in cells.
    Biol Chem 2018 Feb 1. Epub 2018 Feb 1.
    Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA.
    Mitochondrial 2-oxoacid dehydrogenase complexes oxidize 2-oxoglutarate, pyruvate, branched-chain 2-oxoacids and 2-oxoadipate to the corresponding acyl-CoAs and reduce NAD+ to NADH. The isolated enzyme complexes generate superoxide anion radical or hydrogen peroxide in defined reactions by leaking electrons to oxygen. Studies using isolated mitochondria in media mimicking cytosol suggest that the 2-oxoacid dehydrogenase complexes contribute little to the production of superoxide or hydrogen peroxide relative to other mitochondrial sites at physiological steady states. Read More

    The neutral sphingomyelinase 2 in T cell receptor signaling and polarity.
    Biol Chem 2018 Feb 2. Epub 2018 Feb 2.
    Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany.
    By hydrolyzing its substrate sphingomyelin at the cytosolic leaflet of cellular membranes, the neutral sphingomyelinase 2 (NSM2) generates microdomains which serve as docking sites for signaling proteins and thereby, functions to regulate signal relay. This has been particularly studied in cellular stress responses while the regulatory role of this enzyme in the immune cell compartment has only recently emerged. In T cells, phenotypic polarization by co-ordinated cytoskeletal remodeling is central to motility and interaction with endothelial or antigen-presenting cells during tissue recruitment or immune synapse formation, respectively. Read More

    Molecular determinants of Drosophila immunophilin FKBP39 nuclear localization.
    Biol Chem 2018 Feb 6. Epub 2018 Feb 6.
    Department of Biochemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
    FK506-binding proteins (FKBPs) belong to a distinct class of immunophilins that interact with immunosuppressants. They use their peptidyl-prolyl isomerase (PPIase) activity to catalyze the cis-trans conversion of prolyl bonds in proteins during protein-folding events. FKBPs also act as a unique group of chaperones. Read More

    Aβ42 oligomers impair the bioenergetic activity in hippocampal synaptosomes derived from APP-KO mice.
    Biol Chem 2018 Feb 1. Epub 2018 Feb 1.
    Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, Max-von-Laue-Str. 15, D-60438, Frankfurt/Main, Germany.
    Employing hippocampal synaptosomes from amyloid precursor protein (APP)-deleted mice we analyzed the immediate effects of amyloid beta peptide 42 (Aβ42) peptide in its oligomeric or fibrillar assembly or of soluble amyloid precursor protein alpha (sAPPα) protein on their bioenergetic activity. Upon administration of oligomeric Aβ42 peptide for 30 min we observed a robust decrease both in mitochondrial activity and in mitochondrial membrane potential (MMP). In contrast the respective fibrillary or scrambled peptides showed no effect, indicating that inhibition strictly depends on the oligomerization status of the peptide. Read More

    Interaction of the middle domains stabilizes Hsp90α dimer in a closed conformation with high affinity for p23.
    Biol Chem 2018 Jan 26. Epub 2018 Jan 26.
    Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego St., 02-106 Warsaw, Poland.
    The human genome encodes two highly similar cytosolic Hsp90 proteins called isoforms Hsp90α and Hsp90β. Of the 300 client proteins for Hsp90 identified so far only a handful interact specifically with one Hsp90 isoform. Here we report for the first time that Hsp90 cochaperone p23 binds preferentially to Hsp90α and that this interaction is mediated by the middle domain of Hsp90α. Read More

    Metformin-induced anticancer activities: recent insights.
    Biol Chem 2018 Jan 25. Epub 2018 Jan 25.
    Department of Veterinary Physiology and Pharmacology, Texas A&M University, 4466 TAMU, College Station, TX 77843-4466, USA.
    Metformin is a widely used antidiabetic drug, and there is evidence among diabetic patients that metformin is a chemopreventive agent against multiple cancers. There is also evidence in human studies that metformin is a cancer chemotherapeutic agent, and several clinical trials that use metformin alone or in combination with other drugs are ongoing. In vivo and in vitro cancer cell culture studies demonstrate that metformin induces both AMPK-dependent and AMPK-independent genes/pathways that result in inhibition of cancer cell growth and migration and induction of apoptosis. Read More

    Changes of the peripheral blood mononuclear cells membrane fluidity from type 1 Gaucher disease patients: an electron paramagnetic resonance study.
    Biol Chem 2018 Jan 24. Epub 2018 Jan 24.
    EPR Laboratory, Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
    Gaucher disease (GD) is a lysosomal storage disorder, caused by an impaired function of β-glucocerebrosidase, which results in accumulation of glucocerebroside in cells, and altered membrane ordering. Using electron paramagnetic resonance spin labeling, a statistically significant difference in the order parameter between the peripheral blood mononuclear cell membranes of GD patients and healthy controls was observed. Moreover, the results show that the introduction of the enzyme replacement therapy leads to the restoration of the physiological membrane fluidity. Read More

    High-content hydrogen water-induced downregulation of miR-136 alleviates non-alcoholic fatty liver disease by regulating Nrf2 via targeting MEG3.
    Biol Chem 2018 Jan 10. Epub 2018 Jan 10.
    Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan, China.
    This study was aimed to investigate the potential regulatory mechanism of high-content hydrogen water (HHW) in non-alcoholic fatty liver disease (NAFLD). A high-fat diet (HFD)-induced NAFLD mice model and cellular model were prepared. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total cholesterol (TCH) and triglycerides (TG) were measured. Read More

    LncRNA PART1 modulates toll-like receptor pathways to influence cell proliferation and apoptosis in prostate cancer cells.
    Biol Chem 2018 Jan 26. Epub 2018 Jan 26.
    Department of General Surgery, China Medical University Affiliated Shengjing Hospital, No. 36 Sanhao Street, Heping District, Shenyang 110004, Liaoning, China.
    We investigated thoroughly the effect of lncRNA PART1 on prostate cancer cells proliferation and apoptosis, through regulating toll-like receptor (TLR) pathways. LncRNA PART1 expression was also examined by quantitative real-time polymerase chain reactions (qRT-PCR) in human tissues and the cells lines LNCaP and PC3. After transfection with si-PART1 or control constructs, the cell viability was measured by MTS and colony formation assays. Read More

    Biomechanistic insights into the roles of oxidative stress in generating complex neurological disorders.
    Biol Chem 2018 Jan 25. Epub 2018 Jan 25.
    Medicinal Chemistry Department, Qassim University, Qassim 51452, Saudi Arabia.
    Neurological diseases like Alzheimer's disease, epilepsy, parkinsonism, depression, Huntington's disease and amyotrophic lateral sclerosis prevailing globally are considered to be deeply influenced by oxidative stress-based changes in the biochemical settings of the organs. The excess oxygen concentration triggers the production of reactive oxygen species, and even the intrinsic antioxidant enzyme system, i.e. Read More

    How human serum albumin recognizes DNA and RNA.
    Biol Chem 2018 Jan 12. Epub 2018 Jan 12.
    Institute of Chemical Biology and Fundamental Medicine of SB RAS, 8 Lavrentiev Ave., Novosibirsk 630090, Russia.
    We show here for the first time that HSA possesses two nucleic acid-(NA) binding sites and we estimated the relative contributions of the nucleotide links of (pN)n to their total affinity for these binding sites with higher and lower affinity for NAs. The minimal ligands of these binding sites are orthophosphate (Kd=3.0 and 20. Read More

    LncRNA KCNQ1OT1 ameliorates particle-induced osteolysis through inducing macrophage polarization by inhibiting miR-21a-5p.
    Biol Chem 2017 Jun 27. Epub 2017 Jun 27.
    2Department of Orthopedics, The Affiliated Hospital of Xuzhou Medical University, No. 99 Huaihai West Road, Xuzhou 221002, Jiangsu, China.
    This study aimed to investigate the mechanism of lncRNA-KCNQ1OT1 on macrophage polarization to ameliorate particle-induced osteolysis. We used PMMA to induce primary bone marrow-derived macrophages (BMMs) obtained from mice and the RAW 264.7 cell line, and found that the TNF-α concentration and iNOS expression was increased, while IL-10 concentration and Arg1 expression were decreased in PMMA-induced cells. Read More

    The long non-coding RNA CRNDE promotes cervical cancer cell growth and metastasis.
    Biol Chem 2017 12;399(1):93-100
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    This study was intended to analyze effects of lncRNA CRNDE on cervical cancer cell growth and metastasis. Fifty pairs of cervical cancer tissues and corresponding adjacent tissues were collected. Expressions of long non-coding RNAs (lncRNAs) in tissue samples were detected by microarray analysis. Read More

    The role of microRNAs in chronic respiratory disease: recent insights.
    Biol Chem 2018 Feb;399(3):219-234
    Human Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA.
    Chronic respiratory diseases encompass a group of diverse conditions affecting the airways, which all impair lung function over time. They include cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) and asthma, which together affect hundreds of millions of people worldwide. MicroRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional gene repression, are now recognized as major regulators in the development and progression of chronic lung disease. Read More

    Host target-based approaches against arboviral diseases.
    Biol Chem 2018 Feb;399(3):203-217
    Departament of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte 31270-901, Minas Gerais, Brazil.
    In the 20th century, socioeconomic and environmental changes facilitated the reintroduction of mosquitoes in developing cities, resulting in the reinsertion of mosquito-borne viral diseases and the dispersal of their causative agents on a worldwide scale. Recurrent outbreaks of arboviral diseases are being reported, even in regions without a previous history of arboviral disease transmission. Of note, arboviral infections represented approximately 30% of all emerging vector-borne diseases in the last decade. Read More

    Mechanism and dynamics of INPP5E transport into and inside the ciliary compartment.
    Biol Chem 2018 Feb;399(3):277-292
    Structural Biology Group, Max Planck Institute of Molecular Physiology, Otto-Hahn-Straße 11, D-44227 Dortmund, Germany.
    The inositol polyphosphate 5'-phosphatase E (INPP5E) localizes to cilia. We showed that the carrier protein phosphodiesterase 6 delta subunit (PDE6δ) mediates the sorting of farnesylated INPP5E into cilia due to high affinity binding and release by the ADP-ribosylation factor (Arf)-like protein Arl3·GTP. However, the dynamics of INPP5E transport into and inside the ciliary compartment are not fully understood. Read More

    Impact of protamine I on colon cancer proliferation, invasion, migration, diagnosis and prognosis.
    Biol Chem 2018 Feb;399(3):265-275
    Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Jilin 130033, Changchun, China.
    This paper investigates protamine I (PRM1) expression and its effects on proliferation, invasion and migration of colon cancer cells as well as its function in clinical diagnosis and prognosis. Gene chips were used to screen differentially expressed genes. PRM1 expression was detected by Western blotting and quantitative real time-polymerase chain reaction (qRT-PCR). Read More

    TGF-β requires the activation of canonical and non-canonical signalling pathways to induce skeletal muscle atrophy.
    Biol Chem 2018 Feb;399(3):253-264
    Millennium Institute on Immunology and Immunotherapy, 8331150 Santiago, Chile.
    The transforming growth factor type-beta (TGF-β) induces skeletal muscle atrophy characterised by a decrease in the fibre's diameter and levels of myosin heavy chain (MHC), also as an increase of MuRF-1 expression. In addition, TGF-β induces muscle atrophy by a mechanism dependent on reactive oxygen species (ROS). TGF-β signals by activating both canonical Smad-dependent, and non-canonical signalling pathways such as ERK1/2, JNK1/2, and p38 MAPKs. Read More

    Selection of an Anticalin® against the membrane form of Hsp70 via bacterial surface display and its theranostic application in tumour models.
    Biol Chem 2018 Feb;399(3):235-252
    Munich Center for Integrated Protein Science, CIPS-M, and Lehrstuhl für Biologische Chemie, Technische Universität München, D-85354 Freising (Weihenstephan), Germany.
    We describe the selection of Anticalins against a common tumour surface antigen, human Hsp70, using functional display on live Escherichia coli cells as fusion with a truncated EspP autotransporter. While found intracellularly in normal cells, Hsp70 is frequently exposed in a membrane-bound state on the surface of tumour cells and, even more pronounced, in metastases or after radiochemotherapy. Employing a recombinant Hsp70 fragment comprising residues 383-548 as the target, Anticalins were selected from a naïve bacterial library. Read More

    Structure and function of the human parvulins Pin1 and Par14/17.
    Biol Chem 2018 01;399(2):101-125
    Structural and Medicinal Biochemistry, Center for Medical Biotechnology (ZMB), Faculty of Biology, University of Duisburg-Essen, Universitätsstr. 2, D-45117 Essen, Germany.
    Parvulins belong to the family of peptidyl-prolyl cis/trans isomerases (PPIases) assisting in protein folding and in regulating the function of a broad variety of proteins in all branches of life. The human representatives Pin1 and Par14/17 are directly involved in processes influencing cellular maintenance and cell fate decisions such as cell-cycle progression, metabolic pathways and ribosome biogenesis. This review on human parvulins summarizes the current knowledge of these enzymes and intends to oppose the well-studied Pin1 to its less well-examined homolog human Par14/17 with respect to structure, catalytic and cellular function. Read More

    A novel design of HA-coated nanoparticles co-encapsulating plasmid METase and 5-Fu shows enhanced application in targeting gastric cancer stem cells.
    Biol Chem 2018 Feb;399(3):293-303
    Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Donghu District, Nanchang 330006, Jiangxi, China.
    Nanoparticles (NPs) are recognized as an attractive vehicles for cancer treatment due to their targeted drug release. Gastric cancer is an important killer disease, and its therapy methods still need improvement. The NPs were prepared using a precipitation method, and were evaluated using transmission electron microscopy (TEM). Read More

    Structural mechanisms of HECT-type ubiquitin ligases.
    Biol Chem 2018 01;399(2):127-145
    Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Josef-Schneider-Strasse 2, D-97080 Würzburg, Germany.
    Ubiquitin ligases (E3 enzymes) transfer ubiquitin from ubiquitin-conjugating (E2) enzymes to target proteins. By determining the selection of target proteins, modification sites on those target proteins, and the types of ubiquitin modifications that are formed, E3 enzymes are key specificity factors in ubiquitin signaling. Here, I summarize our knowledge of the structural mechanisms in the HECT E3 subfamily, many members of which play important roles in human disease. Read More

    PARP-1 and PARP-2 activity in cancer-induced cachexia: potential therapeutic implications.
    Biol Chem 2018 01;399(2):179-186
    Respiratory Medicine Department, Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, Institute of Medical Research of Hospital del Mar (IMIM)-Hospital del Mar, Parc de Salut Mar, Barcelona Biomedical Research Park (PRBB), Barcelona, Spain.
    Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Read More

    Mechanisms, pathophysiological roles and methods for analyzing mitophagy - recent insights.
    Biol Chem 2018 01;399(2):147-178
    Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.
    In 2012, we briefly summarized the mechanisms, pathophysiological roles and methods for analyzing mitophagy. As then, the mitophagy field has continued to grow rapidly, and many new molecular mechanisms regulating mitophagy and molecular tools for monitoring mitophagy have been discovered and developed. Therefore, the purpose of this review is to update information regarding these advances in mitophagy while focusing on basic molecular mechanisms of mitophagy in different organisms and its pathophysiological roles. Read More

    The inhibition of the mitochondrial F1FO-ATPase activity when activated by Ca2+ opens new regulatory roles for NAD.
    Biol Chem 2018 01;399(2):197-202
    Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, via Tolara di Sopra 50, I-40064 Ozzano dell'Emilia (BO), Italy.
    The mitochondrial F1FO-ATPase is uncompetitively inhibited by NAD+ only when the natural cofactor Mg2+ is replaced by Ca2+, a mode putatively involved in cell death. The Ca2+-dependent F1FO-ATPase is also inhibited when NAD+ concentration in mitochondria is raised by acetoacetate. The enzyme inhibition by NAD+ cannot be ascribed to any de-ac(et)ylation or ADP-ribosylation by sirtuines, as it is not reversed by nicotinamide. Read More

    How to get rid of mitochondria: crosstalk and regulation of multiple mitophagy pathways.
    Biol Chem 2017 12;399(1):29-45
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    Mitochondria are indispensable cellular organelles providing ATP and numerous other essential metabolites to ensure cell survival. Reactive oxygen species (ROS), which are formed as side reactions during oxidative phosphorylation or by external agents, induce molecular damage in mitochondrial proteins, lipids/membranes and DNA. To cope with this and other sorts of organellar stress, a multi-level quality control system exists to maintain cellular homeostasis. Read More

    The dinoponeratoxin peptides from the giant ant Dinoponera quadriceps display in vitro antitrypanosomal activity.
    Biol Chem 2018 01;399(2):187-196
    Faculty of Pharmacy, Department of Clinical and Toxicological Analysis, Federal University of Ceará, Rua Capitão Francisco Pedro 1210, 60430-372 Fortaleza/CE, Brazil.
    The crude venom of the giant ant Dinoponera quadriceps is a cocktail of polypeptides and organic compounds that shows antiparasitic effects against Trypanosoma cruzi, the causative agent of Chagas disease. In order to investigate the venom-derived components responsible for such antitrypanosomal activity, four dinoponeratoxins (DnTxs) were identified, namely M-PONTX-Dq3a, -Dq3b, -Dq3c and -Dq4e, that are diverse in size, net charge, hydrophobicity and propensity to interact with eukaryote cell membranes. These peptides were tested against epimastigote, trypomastigote and amastigote forms of benznidazole (Bz)-resistant Y strain of T. Read More

    Domain topology of human Rasal.
    Biol Chem 2017 12;399(1):63-72
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    Rasal is a modular multi-domain protein of the GTPase-activating protein 1 (GAP1) family; its four known members, GAP1m, Rasal, GAP1IP4BP and Capri, have a Ras GTPase-activating domain (RasGAP). This domain supports the intrinsically slow GTPase activity of Ras by actively participating in the catalytic reaction. In the case of Rasal, GAP1IP4BP and Capri, their remaining domains are responsible for converting the RasGAP domains into dual Ras- and Rap-GAPs, via an incompletely understood mechanism. Read More

    The consequences of deglycosylation of recombinant intra-melanosomal domain of human tyrosinase.
    Biol Chem 2017 12;399(1):73-77
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    Tyrosinase, a melanosomal glycoenzyme, catalyzes initial steps of the melanin biosynthesis. While glycosylation was previously studied in vivo, we present three recombinant mutant variants of human tyrosinase, which were obtained using multiple site-directed mutagenesis, expressed in insect larvae, purified and characterized biochemically. The mutagenesis demonstrated the reduced protein expression and enzymatic activity due to possible loss of protein stability and protein degradation. Read More

    Targeted degradomics in protein terminomics and protease substrate discovery.
    Biol Chem 2017 12;399(1):47-54
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    Targeted degradomics integrates positional information into mass spectrometry (MS)-based targeted proteomics workflows and thereby enables analysis of proteolytic cleavage events with unprecedented specificity and sensitivity. Rapid progress in the establishment of protease-substrate relations provides extensive degradomics target lists that now can be tested with help of selected and parallel reaction monitoring (S/PRM) in complex biological systems, where proteases act in physiological environments. In this minireview, we describe the general principles of targeted degradomics, outline the generic experimental workflow of the methodology and highlight recent and future applications in protease research. Read More

    Maintaining protein composition in cilia.
    Biol Chem 2017 12;399(1):1-11
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    The primary cilium is a sensory organelle that is vital in regulating several signalling pathways. Unlike most organelles cilia are open to the rest of the cell, not enclosed by membranes. The distinct protein composition is crucial to the function of cilia and many signalling proteins and receptors are specifically concentrated within distinct compartments. Read More

    Brain plasticity, cognitive functions and neural stem cells: a pivotal role for the brain-specific neural master gene |-SRGAP2-FAM72-|.
    Biol Chem 2017 12;399(1):55-61
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    Due to an aging society with an increased dementia-induced threat to higher cognitive functions, it has become imperative to understand the molecular and cellular events controlling the memory and learning processes in the brain. Here, we suggest that the novel master gene pair |-SRGAP2-FAM72-| (SLIT-ROBO Rho GTPase activating the protein 2, family with sequence similarity to 72) reveals a new dogma for the regulation of neural stem cell (NSC) gene expression and is a distinctive player in the control of human brain plasticity. Insight into the specific regulation of the brain-specific neural master gene |-SRGAP2-FAM72-| may essentially contribute to novel therapeutic approaches to restore or improve higher cognitive functions. Read More

    Eremophilane-type sesquiterpenes from fungi and their medicinal potential.
    Biol Chem 2017 12;399(1):13-28
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    Eremophilanes are sesquiterpenes with a rearranged carbon skeleton formed both by plants and fungi, however, almost no plant eremophilanes are found in fungi. These eremophilanes possess mainly phytotoxic, antimicrobial, anticancer and immunomodulatory properties and in this review fungal eremophilanes with bioactivities of potential medicinal applications are reviewed and discussed. A special focus is set on natural products bearing highly functionalized fatty acids at C-1 or C-3 position of the eremophilane backbone. Read More

    Regulation of protein function by S-nitrosation and S-glutathionylation: processes and targets in cardiovascular pathophysiology.
    Biol Chem 2017 11;398(12):1267-1293
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    Decades of chemical, biochemical and pathophysiological research have established the relevance of post-translational protein modifications induced by processes related to oxidative stress, with critical reflections on cellular signal transduction pathways. A great deal of the so-called 'redox regulation' of cell function is in fact mediated through reactions promoted by reactive oxygen and nitrogen species on more or less specific aminoacid residues in proteins, at various levels within the cell machinery. Modifications involving cysteine residues have received most attention, due to the critical roles they play in determining the structure/function correlates in proteins. Read More

    Locally produced xenin and the neurotensinergic system in pancreatic islet function and β-cell survival.
    Biol Chem 2017 12;399(1):79-92
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    Modulation of neuropeptide receptors is important for pancreatic β-cell function. Here, islet distribution and effects of the neurotensin (NT) receptor modulators, xenin and NT, was examined. Xenin, but not NT, significantly improved glucose disposal and insulin secretion, in mice. Read More

    Heat shock protein 47 effects on hepatic stellate cell-associated receptors in hepatic fibrosis of Schistosoma japonicum-infected mice.
    Biol Chem 2017 11;398(12):1357-1366
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    The study aimed to explore the regulation of heat shock protein 47 (HSP47) on expressions of receptors associated with hepatic stellate cell (HSC) in liver fibrosis mouse models induced by Schistosoma japonicum (S. japonicum). Mouse fibroblasts (NIH/3T3) were transfected with HSP47 shRNA plasmid by lipofectamine transfection, and experimental fibrosis in HSCs was studied in S. Read More

    Comparison of cytochrome P450 expression in four different human osteoblast models.
    Biol Chem 2017 11;398(12):1327-1334
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    Cytochromes P450 (CYPs) are important for bone homeostasis, but only limited information is available on their expression in human bone cells. We analyzed the expression levels of eight CYPs in osteoblasts cultured in human bone pieces, in osteoblasts differentiated from human periosteum mesenchymal stem cells, in primary human osteoblasts and in the human osteoblast cell line MG63, respectively. Our results confirm previous reports about the presence of CYP11A1, CYP17A1, CYP24A1 and CYP27B1, while demonstrating expression of CYP2E1, CYP26A1, CYP39A1 and CYP51A1 for the first time. Read More

    HDAC1 triggers the proliferation and migration of breast cancer cells via upregulation of interleukin-8.
    Biol Chem 2017 11;398(12):1347-1356
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    Targeted inhibition of histone deacetylase (HDAC) is one of the potent anticancer therapy approaches. Our data showed that mRNA and protein levels of HDAC1 in breast cancer cells were greater than that in normal fibroblast 3T3 cells and normal epithelial breast MCF10A cells. The mRNA levels of HDAC1 in 75% of breast cancer tissues (18/24) were greater than that in their corresponding adjacent normal tissues. Read More

    The molecular mechanisms involved in lectin-induced human platelet aggregation.
    Biol Chem 2017 11;398(12):1335-1346
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    We have compared the effect of three legume lectins, wheat germ agglutinin (WGA), Phaseolus vulgaris agglutinin (PHA) and Lens culinaris agglutinin (LCA), on the function of human platelets. We have found that WGA is more active than PHA in stimulating platelet activation/aggregation, while LCA has no effect. Studies on the mechanisms involved show that WGA and PHA induce phosphorylation/activation of PLCγ2 and increase [Ca2+]i. Read More

    Tissue kallikrein-related peptidase 4 (KLK4), a novel biomarker in triple-negative breast cancer.
    Biol Chem 2017 09;398(10):1151-1164
    Triple-negative breast cancer (TNBC), lacking the steroid hormone receptors ER and PR and the oncoprotein HER2, is characterized by its aggressive pattern and insensitivity to endocrine and HER2-directed therapy. Human kallikrein-related peptidases KLK1-15 provide a rich source of serine protease-type biomarkers associated with tumor growth and cancer progression for a variety of malignant diseases. In this study, recombinant KLK4 protein was generated and affinity-purified KLK4-directed polyclonal antibody pAb587 established to allow localization of KLK4 protein expression in tumor cell lines and archived formalin-fixed, paraffin-embedded TNBC tumor tissue specimens. Read More

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