TY - JOUR A1 - Munter, L.M. A1 - Sieg, H. A1 - Bethge, T. A1 - Liebsch, F. A1 - Bierkandt, Frank A1 - Schleeger, M. A1 - Bittner, H.J. A1 - Heberle, J. A1 - Jakubowski, Norbert A1 - Hildebrand, P.W. A1 - Multhaup, G. T1 - Model peptides uncover the role of the beta-secretase transmembrane sequence in metal ion mediated oligomerization N2 - The β-secretase or β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the enzyme responsible for the formation of amyloid-β peptides, which have a major role in Alzheimer pathogenesis. BACE1 has a transmembrane sequence (TMS), which makes it unique among related proteases. We noticed that the BACE1 TMS contains an uncommon sulfur-rich motif. The sequence MxxxCxxxMxxxCxMxC spans the entire TMS, resembles metal ion binding motifs, and is highly conserved among homologues. We used a synthetic 31-mer model peptide comprising the TMS to study metal ion binding and oligomerization. Applying diverse biochemical and biophysical techniques, we detected dimer and trimer formation of the TMS peptide with copper ions. Replacement of the central Cys466 by Ala essentially abolished these effects. We show that the peptide undergoes a redox reaction with copper ions resulting in a disulfide bridge involving Cys466. Further, we find peptide trimerization that depends on the presence of monovalent copper ions and the sulfhydryl group of Cys466. We identified Cys466 as a key residue for metal ion chelation and to be the core of an oligomerization motif of the BACE1-TMS peptide. Our results demonstrate a novel metal ion controlled oligomerization of the BACE1 TMS, which could have an enormous therapeutic importance against Alzheimer disease. KW - Enzymes KW - Amyloid formation KW - Alzheimer disease KW - Copper PY - 2013 DO - https://doi.org/10.1021/ja410812r SN - 0002-7863 SN - 1520-5126 VL - 135 IS - 51 SP - 19354 EP - 19361 PB - American Chemical Society CY - Washington, DC AN - OPUS4-30543 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Telgmann, L. A1 - Lindner, U. A1 - Lingott, J. A1 - Jakubowski, Norbert T1 - Analysis and speciation of lanthanoides by ICP-MS N2 - Inductively coupled plasma mass spectrometry (ICP-MS) is based on formation of positively charged atomic ions in a high-frequency inductively coupled Argon plasma at atmospheric pressure. The ions are extracted and transferred from the plasma source into a mass analyzer operated at high vacuum via an interface equipped with a sampling and a skimmer cone. The ions are separated in the mass analyzer according to their charge to mass ratio. The ions are converted at a conversion dynode and are detected by use of a secondary electron multiplier or a Faraday cup. From an analytical point of view, ICP-MS is a well-established method for multi-elemental analysis in particular for elements at trace- and ultra-trace levels. Furthermore, methods based on ICP-MS offer simple quantification concepts, for which usually (liquid) standards are applied, low matrix effects compared to other conventional analytical techniques, and relative limits of detection (LODs) in the low pg g−1 range and absolute LODs down to the attomol range. For these applications, ICP-MS excels by a high sensitivity which is independent of the molecular structure and a wide linear dynamic range. It has found acceptance in various application areas and during the last decade ICP-MS is also more and more applied for detection of rare earth elements particularly in the life sciences. Due to the fact that all molecules introduced into the high temperature of the plasma in the ion source were completely dissociated and broken down into atoms, which are subsequently ionized, all elemental species information is completely lost. However, if the different species are separated before they enter the plasma by using adequate fractionation or separation techniques, then ICP-MS can be used as a very sensitive element-specific detector. We will discuss this feature of ICP-MS in this chapter in more detail at hand of the speciation of gadolinium-containing contrast agents. KW - Analysis of lanthanoides KW - ICP-MS KW - Speciation of Gd-containing MRI contrast agents PY - 2016 UR - http://adsabs.harvard.edu/abs/2016PhSRv...1...58T DO - https://doi.org/10.1515/psr-2016-0058 SN - 2365-659X SN - 2365-6581 VL - 1 IS - 11 SP - id. 58, 1 EP - 20 AN - OPUS4-40176 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Richter, Janine A1 - Fettig, Ina A1 - Philipp, Rosemarie A1 - Jakubowski, Norbert T1 - Tributyltin - critical pollutant in whole water samples - development of traceable measurement methods for monitoring under the European water framework directive (WFD) 2000/60/EC N2 - Tributyltin is listed as one of the priority substances in the European Water Framework Directive (WFD). Despite its decreasing input in the environment, it is still present and has to be monitored. In the European Metrology Research Programme project ENV08, a sensitive and reliable analytical method according to the WFD was developed to quantify this environmental pollutant at a very low limit of quantification. With the development of such a primary reference method for tributyltin, the project helped to improve the quality and comparability of monitoring data. An overview of project aims and potential analytical tools is given. KW - Tributyltin KW - European Water Framework Directive KW - Whole water body KW - Reference method PY - 2015 DO - https://doi.org/10.1007/s11356-015-4614-4 SN - 0944-1344 SN - 1614-7499 VL - 22 IS - 13 SP - 9589 EP - 9594 PB - Springer CY - Berlin; Heidelberg AN - OPUS4-33734 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Pedrero, Z. A1 - Murillo, S. A1 - Cámara, C. A1 - Schram, E. A1 - Luten, J.B. A1 - Feldmann, I. A1 - Jakubowski, Norbert A1 - Madrid, Y. T1 - Selenium speciation in different organs of African catfish (Clarias gariepinus) enriched through a selenium-enriched garlic based diet N2 - Speciation of Se in fish is needed to elucidate the metabolism of this element in living organisms in the marine environment. In this paper, selenium concentration and its species distribution in several organs and tissues (liver, gills, kidney, muscle and gastrointestinal tract) of African catfish fed with a selenium-enriched garlic based diet was studied. The intention of this paper is focused on both the investigation of selenium distribution in the soluble protein fraction and the detection of selenoaminoacids. Thus, two different procedures have been developed. In the first procedure, screening of selenium in proteins in the Tris-buffer soluble fraction of different tissues was carried out by size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) after sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) separation and electroblotting onto membranes. For the amino acid analysis, several sample treatments for Se-species extraction, based on enzymatic hydrolysis, were compared. The best results were obtained for incubation at controlled temperature. Application of several sample treatments in conjunction with different chromatographic techniques (reverse phase, anion exchange and ion exchange/size exclusion) was crucial to unambiguous Se-species identification. In Se-enriched African catfish a noticeable increase in the content of selenium in different organs was observed, except for the liver, where the Se level remained unaltered. The kidney was the Se-target organ in animals fed with enriched Se food. Selenomethionine (SeMet) was the main Se species identified in fillet extracts, whereas the presence of selenocysteine (SeCys) was detected in the liver and both SeMet and SeCys were present in the kidney. PY - 2011 DO - https://doi.org/10.1039/c003889j SN - 0267-9477 SN - 1364-5544 VL - 26 IS - 1 SP - 116 EP - 125 PB - Royal Society of Chemistry CY - London AN - OPUS4-22981 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Roos, P.H. A1 - Jakubowski, Norbert T1 - Methods for the discovery of low-abundance biomarkers for urinary bladder cancer in biological fluids N2 - For the study of bladder cancer and the identification of respective tumor markers, blood and, in particular, urine constitute suitable sources of biological material, while both harboring their specific challenges for analytics concerning low-abundance biomarkers. Dissolved proteins and nucleic acids as well as cells and cell-bound molecules can be the analytes. In urine, exfoliated bladder tumor cells have to be identified and in blood, circulating tumor cells have to be detected among huge amounts of other cells. For the detection of both low-abundance cells and molecules, their specific enrichment prior to analysis is advantageous or even necessary. Adapted methods for the analysis of proteomes and subproteomes by 2D-gel electrophoresis, multidimensional chromatography and antibody arrays are discussed. Analysis of nucleic acid-based markers exploits the high amplification power of PCR and modified PCR combined with previous (subtransciptomes) or subsequent (microarray) enrichment to sensitively and specifically detect markers. DNA mutations, DNA-methylation status and apoptotic DNA fragments, as well as levels of ribonucleic acids including microRNAs, can be analyzed by means of these methods. Finally, the challenge of identifying circulating tumor cells and assigning them to their original tissue is critically discussed. PY - 2010 DO - https://doi.org/10.4155/BIO.09.174 SN - 1757-6180 VL - 2 IS - 2 SP - 295 EP - 309 PB - Future Science Group CY - London AN - OPUS4-20981 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Nießner, R. A1 - Broekaert, J.A. A1 - Bron, M. A1 - Einax, J. A1 - Emons, H. A1 - Haisch, C. A1 - Huber, C. A1 - Jakubowski, Norbert A1 - Knopp, D. A1 - Popp, J. A1 - Schäferling, M. T1 - Analytische Chemie 2008/2009 PY - 2010 DO - https://doi.org/10.1002/nadc.201063123 SN - 1439-9598 SN - 1521-3854 VL - 58 IS - 3 SP - 223 EP - 235 PB - Wiley-VCH Verl. CY - Weinheim AN - OPUS4-21177 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Müller, Larissa A1 - Jakubowski, Norbert A1 - Roos, P.H. T1 - Multi-parametric analysis of cytochrome P450 expression in rat liver microsomes by LA-ICP-MS N2 - Quantitative analysis of cytochrome P450 (CYP) patterns of cells and tissues is an important aspect in toxicological and pharmacological research as this group of enzymes is largely involved in the metabolism of toxic compounds and drugs. Here we present a method for the multi-parametric and simultaneous quantitative determination of several cytochromes P450 in liver microsomes of untreated and inducer treated rats. The method is based on the binding of specifically lanthanide labelled antibodies to electrophoretically separated and blotted CYP proteins and their subsequent identification and quantification by LA-ICP-MS. CYP1A1, CYP2B1, CYP2C11, CYP2E1 and CYP3A1 were simultaneously quantified and the patterns between microsomal samples were compared. Microsomes of rats treated with 3-methylcholanthrene, phenobarbital and dexamethasone showed increased levels of CYP1A1, CYP2B1 and CYP3A1, respectively. These results coincide with data obtained by independent methods for CYP quantification, i.e. ethoxyresorufin O-deethylase activity for CYP1A1 and pentoxyresorufin O-depentylase for CYP2B1. The presented method is useful for multi-parametric CYP profiling and has further large potential with respect to the number of analysed parameters/proteins and sensitivity. PY - 2011 DO - https://doi.org/10.1039/c0ja00077a SN - 0267-9477 SN - 1364-5544 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. VL - 26 IS - 2 SP - 310 EP - 319 PB - Royal Society of Chemistry CY - London AN - OPUS4-23465 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Jakubowski, Norbert A1 - Prohaska, T. A1 - Rottmann, L. A1 - Vanhaecke, F. T1 - Inductively coupled plasma- and glow discharge plasma-sector field mass spectrometry - Part I. Tutorial: Fundamentals and instrumentation N2 - The aim of this series of two reviews is to introduce the basic concepts of ICP and GD sector field instruments, to discuss their peculiarities and performance, to present selected analytical applications for demonstration of the 'state of the art' and, finally, to identify possible future trends and developments. Part I focuses on fundamentals, instrumentation and operation of instruments to give an overview of the capabilities of the actual commercially available instrumentation, whereas selected applications will be discussed in detail in part II. PY - 2011 DO - https://doi.org/10.1039/c0ja00161a SN - 0267-9477 SN - 1364-5544 VL - 26 IS - 4 SP - 693 EP - 726 PB - Royal Society of Chemistry CY - London AN - OPUS4-23466 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Jakubowski, Norbert T1 - Inductively coupled plasma- and glow discharge plasma-sector field mass spectrometry - Part II. Applications N2 - Part I of this series of two reviews focused on fundamentals, instrumentation and operation of sector field instruments to give a proper overview of the capabilities of the actual commercially available instrumentation. In part II, selected applications of the last decade are discussed in detail concluding with pinpointing possible future trends and current developments. KW - ICP KW - SF KW - MS PY - 2011 DO - https://doi.org/10.1039/c0ja00007h SN - 0267-9477 SN - 1364-5544 VL - 26 IS - 4 SP - 727 EP - 757 PB - Royal Society of Chemistry CY - London AN - OPUS4-23467 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Roos, P.H. A1 - Jakubowski, Norbert T1 - Cytochromes - fascinating molecular machines N2 - A huge number of functions and reactions can be performed by proteins merely based on their amino acids and their spatial arrangement which results in a specific geometric and electronic environment. The diversity and efficiency of functions, however, can be increased by protein-bound cofactors which fulfil their task in close interaction with the surrounding amino acid side chains. Among these cofactors, metals play an important role. They can be bound to proteins directly via specific amino acids such as cysteine and histidine, for example in zinc finger proteins or in iron sulfur cluster proteins. Another possibility is their integration into the 3D-structure of a protein via a prosthetic group. Porphyrine or porphyrine-like molecules with copper or iron as central bound metal ions constitute important structures in this respect. PY - 2011 DO - https://doi.org/10.1039/c1mt90012a SN - 1756-5901 SN - 1756-591X VL - 3 SP - 316 EP - 318 PB - RSC Publ. CY - Cambridge AN - OPUS4-23830 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -