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  1. Article ; Online: Dumped munitions: New insights into the metabolization of 2,4,6-trinitrotoluene in Baltic flatfish.

    Koske, Daniel / Goldenstein, Nadine I / Rosenberger, Timothy / Machulik, Ulrike / Hanel, Reinhold / Kammann, Ulrike

    Marine environmental research

    2020  Volume 160, Page(s) 104992

    Abstract: Livers from dab (Limanda limanda), plaice (Pleuronectes platessa) and flounder (Platichthys flesus) sampled from the Baltic Sea were used to determine the interaction of flatfish CYP1A enzymes with 2,4,6-trinitrotoluene (TNT) in vitro. Competitive ... ...

    Abstract Livers from dab (Limanda limanda), plaice (Pleuronectes platessa) and flounder (Platichthys flesus) sampled from the Baltic Sea were used to determine the interaction of flatfish CYP1A enzymes with 2,4,6-trinitrotoluene (TNT) in vitro. Competitive inhibition of 7-ethoxyresorufin-O-deethylase (EROD) and 7-methoxyresorufin-O-deethylase (MROD) could be demonstrated for all three flatfish species. The highest inhibition of CYP1A activities was measured in liver samples of flounder resulting in a half maximal inhibitory concentration (IC
    MeSH term(s) Animals ; Cytochrome P-450 CYP1A1 ; Flounder ; Liver ; Trinitrotoluene/pharmacokinetics ; Trinitrotoluene/toxicity ; Water Pollutants, Chemical/pharmacokinetics ; Water Pollutants, Chemical/toxicity
    Chemical Substances Water Pollutants, Chemical ; Trinitrotoluene (118-96-7) ; Cytochrome P-450 CYP1A1 (EC 1.14.14.1)
    Language English
    Publishing date 2020-04-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 1502505-6
    ISSN 1879-0291 ; 0141-1136
    ISSN (online) 1879-0291
    ISSN 0141-1136
    DOI 10.1016/j.marenvres.2020.104992
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Dumped munitions: New insights into the metabolization of 2,4,6-trinitrotoluene in Baltic flatfish

    Koske, Daniel / Goldenstein, Nadine I / Rosenberger, Timothy / Machulik, Ulrike / Hanel, Reinhold / Kammann, Ulrike

    Marine environmental research. 2020 Sept., v. 160

    2020  

    Abstract: Livers from dab (Limanda limanda), plaice (Pleuronectes platessa) and flounder (Platichthys flesus) sampled from the Baltic Sea were used to determine the interaction of flatfish CYP1A enzymes with 2,4,6-trinitrotoluene (TNT) in vitro. Competitive ... ...

    Abstract Livers from dab (Limanda limanda), plaice (Pleuronectes platessa) and flounder (Platichthys flesus) sampled from the Baltic Sea were used to determine the interaction of flatfish CYP1A enzymes with 2,4,6-trinitrotoluene (TNT) in vitro. Competitive inhibition of 7-ethoxyresorufin-O-deethylase (EROD) and 7-methoxyresorufin-O-deethylase (MROD) could be demonstrated for all three flatfish species. The highest inhibition of CYP1A activities was measured in liver samples of flounder resulting in a half maximal inhibitory concentration (IC50) of 28.1 μM TNT. Due to their lower inhibition (EROD IC50 65.2 μM TNT, MROD IC50 40.3 μM TNT), dab liver samples were used to conduct in vitro metabolization experiments with TNT. The metabolization of TNT in fish was investigated with post-mitochondrial fractions (PMF) of dab liver as a model system after adding different cofactors. Rapid and time-dependent enzymatic degradation of TNT was observed. The concentrations of 4-amino-2,6-dinitrotoluene and 2-amino-4,6-dinitrotoluene increased in the samples over time. Additionally, 2,2,6,6-tetranitro-4,4-azoxytoluene was detected in one sample. The results of this study indicate that in vitro experiments are useful to investigate the xenobiotic metabolism of fish under controlled conditions prior to field studies. The metabolites found can serve as target compounds for marine monitoring of TNT contamination in munition dumpsites.
    Keywords Limanda limanda ; Platichthys flesus ; Pleuronectes platessa ; cytochrome P-450 ; enzyme inhibition ; flounder ; in vitro studies ; inhibitory concentration 50 ; liver ; metabolism ; metabolites ; models ; monitoring ; trinitrotoluene ; unspecific monooxygenase ; waste disposal sites ; xenobiotics ; Baltic Sea
    Language English
    Dates of publication 2020-09
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 1502505-6
    ISSN 1879-0291 ; 0141-1136
    ISSN (online) 1879-0291
    ISSN 0141-1136
    DOI 10.1016/j.marenvres.2020.104992
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Dumped munitions

    Koske, Daniel / Goldenstein, Nadine / Rosenberger, Timothy / Machulik, Ulrike / Hanel, Reinhold / Kammann, Ulrike

    New insights into the metabolization of 2,4,6-trinitrotoluene in Baltic flatfish

    2020  

    Abstract: Livers from dab (Limanda limanda), plaice (Pleuronectes platessa) and flounder (Platichthys flesus) sampled from the Baltic Sea were used to determine the interaction of flatfish CYP1A enzymes with 2,4,6-trinitrotoluene (TNT) in vitro. Competitive ... ...

    Abstract Livers from dab (Limanda limanda), plaice (Pleuronectes platessa) and flounder (Platichthys flesus) sampled from the Baltic Sea were used to determine the interaction of flatfish CYP1A enzymes with 2,4,6-trinitrotoluene (TNT) in vitro. Competitive inhibition of 7-ethoxyresorufin-O-deethylase (EROD) and 7-methoxyresorufin-O-deethylase (MROD) could be demonstrated for all three flatfish species. The highest inhibition of CYP1A activities was measured in liver samples of flounder resulting in a half maximal inhibitory concentration (IC50) of 28.1 μM TNT. Due to their lower inhibition (EROD IC50 65.2 μM TNT, MROD IC50 40.3 μM TNT), dab liver samples were used to conduct in vitro metabolization experiments with TNT. The metabolization of TNT in fish was investigated with post-mitochondrial fractions (PMF) of dab liver as a model system after adding different cofactors. Rapid and time-dependent enzymatic degradation of TNT was observed. The concentrations of 4-amino-2,6-dinitrotoluene and 2-amino-4,6-dinitrotoluene increased in the samples over time. Additionally, 2,2,6,6-tetranitro-4,4-azoxytoluene was detected in one sample. The results of this study indicate that in vitro experiments are useful to investigate the xenobiotic metabolism of fish under controlled conditions prior to field studies. The metabolites found can serve as target compounds for marine monitoring of TNT contamination in munition dumpsites.
    Keywords Text ; ddc:570 ; TNT -- In vitro exposition -- Liver -- Flatfish -- Metabolites -- Explosives -- Degradation -- Monitoring
    Subject code 500
    Language English
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Azurin-poly(N-isopropylacrylamide) conjugates by site-directed mutagenesis and their thermosensitive behavior in electron-transfer processes.

    Rosenberger, Nadine / Studer, Armido / Takatani, Nobuyuki / Nakajima, Hiroshi / Watanabe, Yoshihito

    Angewandte Chemie (International ed. in English)

    2009  Volume 48, Issue 11, Page(s) 1946–1949

    Abstract: Searching for "intelligence": Azurin-PNIPAM conjugates were prepared by site-directed mutagenesis followed by protein reconstitution by using imidazole-conjugated poly(N-isopropylacrylamides). The polymer-bound imidazole acts as a ligand in the active ... ...

    Abstract Searching for "intelligence": Azurin-PNIPAM conjugates were prepared by site-directed mutagenesis followed by protein reconstitution by using imidazole-conjugated poly(N-isopropylacrylamides). The polymer-bound imidazole acts as a ligand in the active site of the blue copper protein azurin. The bioconjugates showed thermosensitive behavior in electron-transfer processes with reduced cytochrome c.
    MeSH term(s) Acrylamides/chemical synthesis ; Acrylamides/chemistry ; Acrylic Resins ; Azurin/chemical synthesis ; Azurin/chemistry ; Azurin/genetics ; Circular Dichroism ; Copper/chemistry ; Electron Spin Resonance Spectroscopy ; Electron Transport ; Mutagenesis, Site-Directed ; Polymers/chemical synthesis ; Polymers/chemistry ; Protein Engineering ; Spectrophotometry, Ultraviolet
    Chemical Substances Acrylamides ; Acrylic Resins ; Polymers ; Azurin (12284-43-4) ; poly-N-isopropylacrylamide (25189-55-3) ; Copper (789U1901C5)
    Language English
    Publishing date 2009
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.200804440
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Azurin-Poly(N-isopropylacrylamide) Conjugates by Site-Directed Mutagenesis and their Thermosensitive Behavior in Electron-Transfer Processes

    Rosenberger, Nadine / Studer, Armido / Takatani, Nobuyuki / Nakajima, Hiroshi / Watanabe, Yoshihito

    Angewandte Chemie. 2009 Mar. 02, v. 48, no. 11

    2009  

    Abstract: Searching for "intelligence": Azurin-PNIPAM conjugates were prepared by site-directed mutagenesis followed by protein reconstitution by using imidazole-conjugated poly(N-isopropylacrylamides). The polymer-bound imidazole acts as a ligand in the active ... ...

    Abstract Searching for "intelligence": Azurin-PNIPAM conjugates were prepared by site-directed mutagenesis followed by protein reconstitution by using imidazole-conjugated poly(N-isopropylacrylamides). The polymer-bound imidazole acts as a ligand in the active site of the blue copper protein azurin. The bioconjugates showed thermosensitive behavior in electron-transfer processes with reduced cytochrome c.
    Language English
    Dates of publication 2009-0302
    Size p. 1946-1949.
    Publishing place Wiley-VCH Verlag
    Document type Article
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.200804440
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Histone deacetylase inhibitor-induced sensitization to TNFalpha/TRAIL-mediated apoptosis in cervical carcinoma cells is dependent on HPV oncogene expression.

    Darvas, Katalin / Rosenberger, Simone / Brenner, Dirk / Fritsch, Cornelius / Gmelin, Nadine / Krammer, Peter H / Rösl, Frank

    International journal of cancer

    2010  Volume 127, Issue 6, Page(s) 1384–1392

    Abstract: Histone-deacetylase (HDAC) inhibitors (HDACi) can block proliferation and induce intrinsic apoptosis in human papillomavirus (HPV)-positive cervical carcinoma cells, independently of copy number and integration locus of the viral DNA. Using HPV18- ... ...

    Abstract Histone-deacetylase (HDAC) inhibitors (HDACi) can block proliferation and induce intrinsic apoptosis in human papillomavirus (HPV)-positive cervical carcinoma cells, independently of copy number and integration locus of the viral DNA. Using HPV18-positive HeLa cells as model systems, we provide evidence that HDAC inhibition leads to transcriptional suppression of c-FLIP, which negatively regulates extrinsic apoptosis by preventing the recruitment of caspase-8 to the death-inducing signaling complex. Consequently, HDACi pretreatment renders cervical cancer cells sensitive to TNFalpha and TRAIL-induced apoptosis. Already 5-hr incubation with TNFalpha or TRAIL was sufficient to eradicate more than 40% of pretreated cells, which are normally completely refractory against respective death-ligands alone even under long-term incubation. Ectopic expression of either short or long splicing variant of c-FLIP, c-FLIP(s) and c-FLIP(L), abrogates sensitization. Notably, combined HDACi/death ligand treatment did not result in eradication of HPV-negative cells, despite the fact that both c-FLIP isoforms were also downregulated. However, knocking down HPV18 E6/E7 transcription by siRNA prevents HDACi/death-ligand mediated apoptosis, indicating that continued viral oncogene expression favors sensitization. Here, the viral oncoprotein E7 seems to play a functional role, since only HPV16 E7-immortalized human keratinocytes underwent significant apoptosis on HDACi/TNFalpha treatment, whereas keratinocytes expressing only HPV16 E6 or primary keratinocytes were refractory under the same experimental conditions. Taken together, HDACi can be considered as an alternative therapeutic option in the treatment of premalignant and malignant lesions.
    MeSH term(s) Alphapapillomavirus/genetics ; Apoptosis/drug effects ; Blotting, Western ; Female ; Flow Cytometry ; HeLa Cells ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Oncogenes ; Reverse Transcriptase Polymerase Chain Reaction ; TNF-Related Apoptosis-Inducing Ligand/physiology ; Tumor Necrosis Factor-alpha/physiology ; Uterine Cervical Neoplasms/pathology ; Uterine Cervical Neoplasms/virology
    Chemical Substances Histone Deacetylase Inhibitors ; TNF-Related Apoptosis-Inducing Ligand ; TNFSF10 protein, human ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2010-09-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.25170
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  7. Article ; Online: Activation of hypoxia inducible factor 1 is a general phenomenon in infections with human pathogens.

    Werth, Nadine / Beerlage, Christiane / Rosenberger, Christian / Yazdi, Amir S / Edelmann, Markus / Amr, Amro / Bernhardt, Wanja / von Eiff, Christof / Becker, Karsten / Schäfer, Andrea / Peschel, Andreas / Kempf, Volkhard A J

    PloS one

    2010  Volume 5, Issue 7, Page(s) e11576

    Abstract: Background: Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases.: ...

    Abstract Background: Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases.
    Methodology/principal findings: Using patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i) in all ex vivo in biopsies of patients suffering from skin infections, (ii) in vitro using cell culture infection models and (iii) in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs) of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis.
    Conclusions/significance: Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections.
    MeSH term(s) Animals ; Cell Hypoxia/genetics ; Cell Hypoxia/physiology ; Cell Line ; Female ; HeLa Cells ; Humans ; Hypoxia-Inducible Factor 1/genetics ; Hypoxia-Inducible Factor 1/metabolism ; Immunohistochemistry ; In Vitro Techniques ; Mice ; Oxygen Consumption ; Peritonitis/metabolism ; Peritonitis/microbiology ; Reverse Transcriptase Polymerase Chain Reaction ; Skin Diseases, Infectious/metabolism ; Staphylococcus aureus/pathogenicity ; Transcriptional Activation/genetics ; Transcriptional Activation/physiology
    Chemical Substances Hypoxia-Inducible Factor 1
    Language English
    Publishing date 2010-07-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0011576
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  8. Article ; Online: Activation of hypoxia inducible factor 1 is a general phenomenon in infections with human pathogens.

    Nadine Werth / Christiane Beerlage / Christian Rosenberger / Amir S Yazdi / Markus Edelmann / Amro Amr / Wanja Bernhardt / Christof von Eiff / Karsten Becker / Andrea Schäfer / Andreas Peschel / Volkhard A J Kempf

    PLoS ONE, Vol 5, Iss 7, p e

    2010  Volume 11576

    Abstract: BACKGROUND: Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases. ... ...

    Abstract BACKGROUND: Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases. METHODOLOGY/PRINCIPAL FINDINGS: Using patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i) in all ex vivo in biopsies of patients suffering from skin infections, (ii) in vitro using cell culture infection models and (iii) in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs) of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis. CONCLUSIONS/SIGNIFICANCE: Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2010-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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