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Article ; Online: Lipid glycosylation: a primer for histochemists and cell biologists.

Kopitz, Jürgen

2017 Volume 147, Issue 2, Page(s) 175–198

Abstract: Glycolipids are glycoconjugates that are predominantly found on the extracellular surface of cells ranging from bacteria to men. In bacteria and plants, glycoglycerolipids represent the main glycolipid species. Ceramides as carrier for glycans, termed ... ...

Abstract	Glycolipids are glycoconjugates that are predominantly found on the extracellular surface of cells ranging from bacteria to men. In bacteria and plants, glycoglycerolipids represent the main glycolipid species. Ceramides as carrier for glycans, termed glycosphingolipids (GSLs), are characteristic for vertebrates and insects. The glycan part is involved in a variety of biological activities including cell adhesion and initiation of signaling. Most of these functions rest on two basic principles: (1) GSLs spontaneously contribute to organize lipid rafts in biological membranes, thereby forming functional complexes ('glycosynapses') with receptor proteins and ion channels and (2) their glycans are bound by receptors like galectins (protein-glycan recognition) or cognate glycans (glycan-glycan recognition). This interaction modulates cell adhesion, differentiation and growth processes. Besides their contribution to normal cell behavior, GSL expression patterns also influence disease processes by inducing cellular malfunctions when aberrant, as highlighted by inherited disorders of GSL metabolism like sphingolipidoses. Altered GSL patterns are also associated with common neurological diseases, autoimmune diseases and cancer. With respect to infections, various GSL-presented glycans are attachment sites for bacteria and viruses as well as primary targets for bacterial toxins. This review provides an introduction to GSL structures, their nomenclature and metabolism. Building on this, normal and pathological functions of GSL will be surveyed.
MeSH term(s)	Cell Adhesion ; Cell Biology ; Glycolipids/chemistry ; Glycolipids/metabolism ; Glycosylation ; Humans ; Lipid Metabolism ; Lipids/chemistry
Chemical Substances	Glycolipids ; Lipids ; glycerolglycolipids
Language	English
Publishing date	2017-02
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1222930-1
ISSN	1432-119X ; 0301-5564 ; 0948-6143
ISSN (online)	1432-119X
ISSN	0301-5564 ; 0948-6143
DOI	10.1007/s00418-016-1518-4
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Article ; Online: Correction to: Proinflammatory Extracellular Vesicle-Mediated Signaling Contributes to the Induction of Neuroinflammation in Animal Models of Endotoxemia and Peripheral Surgical Stress.

Fricke, F / Gebert, J / Kopitz, J / Plaschke, K

Cellular and molecular neurobiology

2021 Volume 41, Issue 6, Page(s) 1337

Language	English
Publishing date	2021-06-08
Publishing country	United States
Document type	Published Erratum
ZDB-ID	283404-2
ISSN	1573-6830 ; 0272-4340
ISSN (online)	1573-6830
ISSN	0272-4340
DOI	10.1007/s10571-021-01112-4
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Zs.A 1727: Show issues

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Article ; Online: Proteomic Analysis Reveals Potential Exosomal Biomarkers in Patients With Sporadic Alzheimer Disease.

Plaschke, Konstanze / Kopitz, Jürgen / Gebert, Johannes / Wolf, Nadine D / Wolf, Robert Christian

Alzheimer disease and associated disorders

2023 Volume 37, Issue 4, Page(s) 315–321

Abstract: Background: Despite substantial progress made in the past decades, the pathogenesis of sporadic Alzheimer disease (sAD) and related biological markers of the disease are still controversially discussed. Cerebrospinal fluid and functional brain imaging ... ...

Abstract	Background: Despite substantial progress made in the past decades, the pathogenesis of sporadic Alzheimer disease (sAD) and related biological markers of the disease are still controversially discussed. Cerebrospinal fluid and functional brain imaging markers have been established to support the clinical diagnosis of sAD. Yet, due to the invasiveness of such diagnostics, less burdensome markers have been increasingly investigated in the past years. Among such markers, extracellular vesicles may yield promise in (early) diagnostics and treatment monitoring in sAD. Materials and methods: In this pilot study, we collected the blood plasma of 18 patients with sAD and compared the proteome of extracted extracellular vesicles with the proteome of 11 age-matched healthy controls. The resulting proteomes were characterized by Gene Ontology terms and between-group statistics. Results: Ten distinct proteins were found to significantly differ between sAD patients and controls (P<0.05, False Discovery Rate, corrected). These proteins included distinct immunoglobulins, fibronectin, and apolipoproteins. Conclusions: These findings lend further support for exosomal changes in neurodegenerative disorders, and particularly in sAD. Further proteomic research could decisively advance our knowledge of sAD pathophysiology as much as it could foster the development of clinically meaningful biomarkers.
MeSH term(s)	Humans ; Alzheimer Disease/diagnosis ; Pilot Projects ; Proteome ; Proteomics ; Biomarkers
Chemical Substances	Proteome ; Biomarkers
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1002700-2
ISSN	1546-4156 ; 0893-0341
ISSN (online)	1546-4156
ISSN	0893-0341
DOI	10.1097/WAD.0000000000000589
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Article ; Online: Development and Pilot Testing of an Algorithm-Based Approach to Anticholinergic Deprescribing in Older Patients.

Wehran, Tanja / Eidam, Annette / Czock, David / Kopitz, Jürgen / Plaschke, Konstanze / Mattern, Margarete / Haefeli, Walter Emil / Bauer, Jürgen Martin / Seidling, Hanna Marita

Drugs & aging

2024 Volume 41, Issue 2, Page(s) 153–164

Abstract: Background: Adverse anticholinergic drug reactions are common, yet evidence on how to reduce exposure to anticholinergic activity and reliably measure successful deprescribing is still scant. This study proposes an algorithm-based approach to evaluate ... ...

Abstract	Background: Adverse anticholinergic drug reactions are common, yet evidence on how to reduce exposure to anticholinergic activity and reliably measure successful deprescribing is still scant. This study proposes an algorithm-based approach to evaluate and reduce anticholinergic load, and reports the results of its pilot testing. Methods: Based on published evidence and expert opinion, a list of 85 anticholinergic drugs and 21 algorithms for reducing anticholinergic load, e.g., by recommending alternative drugs with lower risk, were developed. An accompanying test battery was assembled by focusing on instruments that sensitively reflect anticholinergic load and may be sensitive to depict changes (Neuropsychological Assessment Battery to measure memory and attention, validated assessments for constipation, urinary symptoms, and xerostomia, as well as blood biomarkers). The approach was pilot-tested in a geriatric rehabilitation unit, with clinician feedback as the primary outcome and characterization of anticholinergic symptoms as the secondary outcome. The intervention was delivered by a pharmacist and a clinical pharmacologist who used the algorithms to generate personalized recommendation letters. Results: We included a total of 20 patients, 13 with anticholinergic drugs and 7 without. Recommendations were made for 22 drugs in nine patients from the intervention group, of which seven letters (78%) were considered helpful and 8/22 (36%) anticholinergic drugs were discontinued, reducing anticholinergic load in seven patients. In contrast to patients without drug change, memory assessment in patients with reduced anticholinergic load improved significantly after 2 weeks (6 ± 3 vs. -1 ± 6 points). Conclusions: The approach was well received by the participating physicians and might support standardized anticholinergic deprescribing.
MeSH term(s)	Humans ; Aged ; Cholinergic Antagonists/adverse effects ; Deprescriptions ; Patients ; Physicians ; Constipation/chemically induced
Chemical Substances	Cholinergic Antagonists
Language	English
Publishing date	2024-02-06
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	1075770-3
ISSN	1179-1969 ; 1170-229X
ISSN (online)	1179-1969
ISSN	1170-229X
DOI	10.1007/s40266-023-01089-3
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Article ; Online: Proinflammatory Extracellular Vesicle-Mediated Signaling Contributes to the Induction of Neuroinflammation in Animal Models of Endotoxemia and Peripheral Surgical Stress.

Fricke, F / Gebert, J / Kopitz, J / Plaschke, K

Cellular and molecular neurobiology

2020 Volume 41, Issue 6, Page(s) 1325–1336

Abstract: Peripheral inflammation induced by endotoxemia or surgical stress induces neuroinflammation thereby causing neurological symptoms ranging from sickness behavior to delirium. Thus, proinflammatory signaling must be operative between the periphery and the ... ...

Abstract	Peripheral inflammation induced by endotoxemia or surgical stress induces neuroinflammation thereby causing neurological symptoms ranging from sickness behavior to delirium. Thus, proinflammatory signaling must be operative between the periphery and the central nervous system (CNS). In the present study, we tested whether nanometer-sized extracellular vesicles (EVs) that were produced during the peripheral inflammatory process have the capacity to induce neuroinflammation. Conditions of endotoxemia or surgical intervention were simulated in rats by lipopolysaccharide (LPS) injection or partial hepatectomy (HpX). EVs were concentrated from these animals and tested for their proinflammatory action (I) in a microglial cell line and (II) by intracerebroventricular and (III) by intravenous injections into healthy rats. EVs from both conditions induced the secretion of cytokines from the glial cell line. Intracerebroventricular injection of the EVs caused the release of inflammatory cytokines to the cerebrospinal fluid indicating their pro-neuroinflammatory capacity. Finally, proinflammatory EVs were shown to pass the blood-brain barrier and induce neuroinflammation after their intravenous injection. Based on these data, we suggest that EV-associated proinflammatory signaling contributes to the induction of neuroinflammation in endotoxemia and peripheral surgical stress. Preliminary results suggest that peripheral cholinergic signals might be involved in the control of proinflammatory EV-mediated signaling from the periphery to the brain.
MeSH term(s)	Animals ; Disease Models, Animal ; Endotoxemia/chemically induced ; Endotoxemia/metabolism ; Extracellular Vesicles/drug effects ; Extracellular Vesicles/metabolism ; Humans ; Inflammation Mediators/metabolism ; Lipopolysaccharides/toxicity ; Male ; Microglia/drug effects ; Microglia/metabolism ; Neuroinflammatory Diseases/chemically induced ; Neuroinflammatory Diseases/metabolism ; Rats ; Rats, Wistar ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Surgical Wound/metabolism
Chemical Substances	Inflammation Mediators ; Lipopolysaccharides
Language	English
Publishing date	2020-06-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	283404-2
ISSN	1573-6830 ; 0272-4340
ISSN (online)	1573-6830
ISSN	0272-4340
DOI	10.1007/s10571-020-00905-3
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Article ; Online: Low-sulphate water sample preparation for LSC detection of

Schubert, M / Kopitz, J / Knöller, K

Journal of environmental radioactivity

2020 Volume 213, Page(s) 106153

Abstract: Information about groundwater residence times is essential for evaluating appropriate groundwater abstraction rates and aquifer vulnerabilities and hence for sustainable groundwater management in general. Naturally occurring radionuclides are suitable ... ...

Abstract	Information about groundwater residence times is essential for evaluating appropriate groundwater abstraction rates and aquifer vulnerabilities and hence for sustainable groundwater management in general. Naturally occurring radionuclides are suitable tools for related investigations. While the applicability of several long-lived radionuclides for the investigation of long-term processes has been demonstrated frequently, residence times of less than one year are only scarcely discussed in the literature. That is due to the rather small number of applicable radionuclides that show adequately short half-lives. A promising approach for investigating sub-yearly residence times applies radioactive sulphur.
MeSH term(s)	Groundwater/chemistry ; Radiation Monitoring ; Radioisotopes ; Sulfates ; Water Pollutants, Radioactive
Chemical Substances	Radioisotopes ; Sulfates ; Water Pollutants, Radioactive
Language	English
Publishing date	2020-01-01
Publishing country	England
Document type	Journal Article
ZDB-ID	1483112-0
ISSN	1879-1700 ; 0265-931X
ISSN (online)	1879-1700
ISSN	0265-931X
DOI	10.1016/j.jenvrad.2019.106153
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Article ; Online: Combining Recombinase-Mediated Cassette Exchange Strategy with Quantitative Proteomic and Phosphoproteomic Analyses to Inspect Intracellular Functions of the Tumor Suppressor Galectin-4 in Colorectal Cancer Cells.

Michalak, Malwina / Golde, Viola / Helm, Dominik / Kaltner, Herbert / Gebert, Johannes / Kopitz, Jürgen

International journal of molecular sciences

2022 Volume 23, Issue 12

Abstract: Galectin-4 (Gal4) has been suggested to function as a tumor suppressor in colorectal cancer (CRC). In order to systematically explore its function in CRC, we established a CRC cell line where Gal4 expression can be regulated via the doxycycline (dox)- ... ...

Abstract	Galectin-4 (Gal4) has been suggested to function as a tumor suppressor in colorectal cancer (CRC). In order to systematically explore its function in CRC, we established a CRC cell line where Gal4 expression can be regulated via the doxycycline (dox)-inducible expression of a single copy wildtype
MeSH term(s)	Cell Line, Tumor ; Colorectal Neoplasms/pathology ; DNA-Binding Proteins ; Forkhead Transcription Factors ; Galectin 4 ; Humans ; Intracellular Space/metabolism ; Proteomics/methods ; Recombinases ; Transcription Factors
Chemical Substances	DNA-Binding Proteins ; FOXK1 protein, human ; Forkhead Transcription Factors ; Galectin 4 ; Recombinases ; Transcription Factors ; ZBTB7A protein, human
Language	English
Publishing date	2022-06-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23126414
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Article ; Online: Improved approach for LSC detection of

Schubert, M / Kopitz, J / Knöller, K

Journal of environmental radioactivity

2019 Volume 208-209, Page(s) 106022

Abstract: The knowledge of groundwater residence times in (vulnerable) aquifers is essential for the sustainable management of the associated groundwater resources. A powerful tool for related investigations is the application of naturally occurring radioisotopes ... ...

Abstract	The knowledge of groundwater residence times in (vulnerable) aquifers is essential for the sustainable management of the associated groundwater resources. A powerful tool for related investigations is the application of naturally occurring radioisotopes as water age indicators. However, due to the limited number of suitable (i.e. omnipresent, short-lived and easily detectable) radionuclides only few studies focus on groundwater ages below one year. A natural radionuclide that does have the potential to cover this time range is
MeSH term(s)	Groundwater/chemistry ; Radiation Monitoring/methods ; Scintillation Counting ; Sulfur Radioisotopes/analysis ; Water Pollutants, Radioactive/analysis
Chemical Substances	Sulfur Radioisotopes ; Water Pollutants, Radioactive
Language	English
Publishing date	2019-07-24
Publishing country	England
Document type	Journal Article
ZDB-ID	1483112-0
ISSN	1879-1700 ; 0265-931X
ISSN (online)	1879-1700
ISSN	0265-931X
DOI	10.1016/j.jenvrad.2019.106022
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Article ; Online: Combining Click Chemistry-Based Proteomics With Dox-Inducible Gene Expression.

Gebert, J / Schnölzer, M / Warnken, U / Kopitz, J

Methods in enzymology

2017 Volume 585, Page(s) 295–327

Abstract: Inactivating mutations in single genes can trigger, prevent, promote, or alleviate diseases. Identifying such disease-related genes is a main pillar of medical research. Since proteins play a crucial role in mediating these effects, their impact on the ... ...

Abstract	Inactivating mutations in single genes can trigger, prevent, promote, or alleviate diseases. Identifying such disease-related genes is a main pillar of medical research. Since proteins play a crucial role in mediating these effects, their impact on the diseased cells' proteome including posttranslational modifications has to be elucidated for a detailed understanding of the role of these genes in the disease process. In complex disorders, like cancer, several genes contribute to the disease process, thereby hampering the assignment of a proteomic change to the corresponding causative gene. To enable comprehensive screening for the impact of inactivation of a gene, e.g., loss of a tumor suppressor in cancer, on the cellular proteome, we present a strategy based on combination of three technologies that is recombinase-mediated cassette exchange, click chemistry, and mass spectrometry. The methodology is exemplified by the analysis of the proteomic changes induced by the loss of a tumor suppressor gene in colorectal cancer cells. To demonstrate the applicability to screen for posttranslational modification changes, we also describe the analysis of protein glycosylation changes caused by the tumor suppressor inactivation. In principle, this strategy can be applied to analyze the effects of any gene of interest on protein expression as well as posttranslational modification by glycosylation. Moreover adaptation of the strategy to an appropriate cell culture model has the potential for application on a broad range of diseases where the disease-promoting mutations have been identified.
MeSH term(s)	Animals ; Biotin/chemistry ; Click Chemistry/methods ; Doxorubicin/chemistry ; Humans ; Protein Processing, Post-Translational ; Proteome/chemistry ; Proteomics/methods
Chemical Substances	Proteome ; Biotin (6SO6U10H04) ; Doxorubicin (80168379AG)
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1557-7988 ; 0076-6879
ISSN (online)	1557-7988
ISSN	0076-6879
DOI	10.1016/bs.mie.2016.09.022
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Article ; Online: Lectinology 4.0: Altering modular (ga)lectin display for functional analysis and biomedical applications.

Ludwig, Anna-Kristin / Kaltner, Herbert / Kopitz, Jürgen / Gabius, Hans-Joachim

Biochimica et biophysica acta. General subjects

2019 Volume 1863, Issue 5, Page(s) 935–940

Abstract: Background: Recognition of glycans by lectins is emerging as (patho)physiologically broadly used mode of cellular information transfer. Whereas the direct ligand-receptor contact is often already thoroughly characterized, the functional relevance of ... ...

Abstract	Background: Recognition of glycans by lectins is emerging as (patho)physiologically broadly used mode of cellular information transfer. Whereas the direct ligand-receptor contact is often already thoroughly characterized, the functional relevance of aspects of architecture such as modular design and valence of lectins is less well defined. Scope of review: Following an introduction to modular lectin design, three levels of methodology are then reviewed that delineate lectin structure-activity relationships beyond glycan binding, with emphasis on domain shuffling. Major conclusions: Engineering of variants by modular transplantation facilitates versatile Nature-inspired design switches and access to new combinations with translational potential, as exemplified for human adhesion/growth-regulatory galectins. General significance: To gain an understanding of the functional significance of natural variations in quaternary structure and modular design within a protein family is a current challenge. Strategic application of methods of the described phases is a means to respond to this challenge.
MeSH term(s)	Biomedical Research ; Galectins/chemistry ; Galectins/metabolism ; Humans ; Polysaccharides/chemistry ; Polysaccharides/metabolism ; Protein Engineering ; Structure-Activity Relationship
Chemical Substances	Galectins ; Polysaccharides
Language	English
Publishing date	2019-03-06
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	60-7
ISSN	1872-8006 ; 1879-2596 ; 1879-260X ; 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)	1872-8006 ; 1879-2596 ; 1879-260X ; 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.2019.03.005
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