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  1. Article ; Online: A large travel-associated outbreak of iatrogenic botulism in four European countries following intragastric botulinum neurotoxin injections for weight reduction, Türkiye, February to March 2023.

    Dorner, Martin Bernhard / Wilking, Hendrik / Skiba, Martin / Wilk, Laura / Steinberg, Maximilian / Worbs, Sylvia / Çeken, Sabahat / Kaygusuz, Sedat / Simon, Stéphanie / Becher, François / Mikolajewska, Agata / Kornschober, Christian / Bütler, Timo / Jourdan-Da-Silva, Nathalie / An der Heiden, Maria / Schaade, Lars / Stark, Klaus / Dorner, Brigitte Gertrud / Frank, Christina

    Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin

    2023  Volume 28, Issue 23

    Abstract: In March 2023, 34 associated cases of iatrogenic botulism were detected in Germany (30 cases), Switzerland (two cases), Austria (one case), and France (one case). An alert was rapidly disseminated via European Union networks and communication platforms ( ... ...

    Abstract In March 2023, 34 associated cases of iatrogenic botulism were detected in Germany (30 cases), Switzerland (two cases), Austria (one case), and France (one case). An alert was rapidly disseminated via European Union networks and communication platforms (Food- and Waterborne Diseases and Zoonoses Network, EpiPulse, Early Warning and Response System) and the International Health Regulation mechanism; the outbreak was investigated in a European collaboration. We traced sources of the botulism outbreak to treatment of weight loss in Türkiye, involving intragastric injections of botulinum neurotoxin. Cases were traced using a list of patients who had received this treatment. Laboratory investigations of the first 12 German cases confirmed nine cases. The application of innovative and highly sensitive endopeptidase assays was necessary to detect minute traces of botulinum neurotoxin in patient sera. The botulism notification requirement for physicians was essential to detect this outbreak in Germany. The surveillance case definition of botulism should be revisited and inclusion of cases of iatrogenic botulism should be considered as these cases might lack standard laboratory confirmation yet warrant public health action. Any potential risks associated with the use of botulinum neurotoxins in medical procedures need to be carefully balanced with the expected benefits of the procedure.
    MeSH term(s) Animals ; Humans ; Botulinum Toxins/adverse effects ; Botulism/diagnosis ; Botulism/epidemiology ; Botulism/etiology ; Neurotoxins ; Travel ; Disease Outbreaks ; Weight Loss ; Iatrogenic Disease/epidemiology ; Clostridium botulinum
    Chemical Substances Botulinum Toxins (EC 3.4.24.69) ; Neurotoxins
    Language English
    Publishing date 2023-06-08
    Publishing country Sweden
    Document type Journal Article
    ZDB-ID 1338803-4
    ISSN 1560-7917 ; 1025-496X
    ISSN (online) 1560-7917
    ISSN 1025-496X
    DOI 10.2807/1560-7917.ES.2023.28.23.2300203
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Protection of dystrophic muscle cells with polyphenols from green tea correlates with improved glutathione balance and increased expression of 67LR, a receptor for (-)-epigallocatechin gallate.

    Dorchies, Olivier M / Wagner, Stéphanie / Buetler, Timo M / Ruegg, Urs T

    BioFactors (Oxford, England)

    2009  Volume 35, Issue 3, Page(s) 279–294

    Abstract: Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease caused by the absence of the protein dystrophin. Because oxidative stress contributes to the pathogenesis of DMD, we investigated if a green tea polyphenol blend (GTP) and its major ... ...

    Abstract Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease caused by the absence of the protein dystrophin. Because oxidative stress contributes to the pathogenesis of DMD, we investigated if a green tea polyphenol blend (GTP) and its major polyphenol (-)-epigallocatechin gallate (EGCg), could protect muscle cell primary cultures from oxidative damage induced by hydrogen peroxide (H(2)O(2)) in the widely used mdx mouse model. On-line fluorimetric measurements using an H(2)O(2)-sensitive probe indicated that GTP and EGCg scavenged peroxide in a concentration-dependent manner. A 48 h exposure to EGCg increased glutathione content but did not alter the expression of proteins involved in membrane stabilization and repair. Pretreatment of dystrophic cultures with GTP or EGCg 48 h before exposure to H(2)O(2) improved cell survival. Normal cultures were protected by GTP but not by EGCg. 67LR, a receptor for EGCg, was seven times more abundant in dystrophic compared with normal cultures. Altogether our results demonstrate that GTP and EGCg protect muscle cells by scavenging H(2)O(2) and by improving the glutathione balance. In addition, the higher levels of 67LR in dystrophic muscle cells compared with normal ones likely contribute to EGCg-mediated survival.
    MeSH term(s) Animals ; Animals, Newborn ; Catechin/analogs & derivatives ; Catechin/pharmacology ; Cell Survival/drug effects ; Cells, Cultured ; Flavonoids/pharmacology ; Glutathione/metabolism ; Hydrogen Peroxide/pharmacology ; Immunohistochemistry ; Mice ; Mice, Inbred C57BL ; Mice, Inbred mdx ; Mice, Mutant Strains ; Muscle Cells/drug effects ; Muscle Cells/metabolism ; Muscle, Skeletal/cytology ; Oxidative Stress/drug effects ; Phenols/pharmacology ; Polyphenols ; Protease Inhibitors/pharmacology ; Receptors, Laminin/metabolism ; Tea/chemistry
    Chemical Substances Flavonoids ; Phenols ; Polyphenols ; Protease Inhibitors ; Receptors, Laminin ; Tea ; Catechin (8R1V1STN48) ; Hydrogen Peroxide (BBX060AN9V) ; epigallocatechin gallate (BQM438CTEL) ; Glutathione (GAN16C9B8O)
    Language English
    Publishing date 2009-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 59230-4
    ISSN 1872-8081 ; 0951-6433
    ISSN (online) 1872-8081
    ISSN 0951-6433
    DOI 10.1002/biof.34
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Role of superoxide as a signaling molecule.

    Buetler, Timo M / Krauskopf, Alexandra / Ruegg, Urs T

    News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society

    2004  Volume 19, Page(s) 120–123

    Abstract: Superoxide is known to affect vascular physiology in several ways and has also been recognized to contribute significantly to vascular physiopathology. Here we discuss the emerging role of superoxide as an essential signaling molecule in normal ... ...

    Abstract Superoxide is known to affect vascular physiology in several ways and has also been recognized to contribute significantly to vascular physiopathology. Here we discuss the emerging role of superoxide as an essential signaling molecule in normal physiology.
    MeSH term(s) Animals ; Cell Division/physiology ; Humans ; Signal Transduction/physiology ; Superoxides/metabolism
    Chemical Substances Superoxides (11062-77-4)
    Language English
    Publishing date 2004-05-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 632842-8
    ISSN 1522-161X ; 0886-1714
    ISSN (online) 1522-161X
    ISSN 0886-1714
    DOI 10.1152/nips.01514.2003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Dicarbonyls stimulate cellular protection systems in primary rat hepatocytes and show anti-inflammatory properties.

    Buetler, Timo M / Latado, Hélia / Baumeyer, Alexandra / Delatour, Thierry

    Annals of the New York Academy of Sciences

    2008  Volume 1126, Page(s) 113–117

    Abstract: Advanced glycation endproducts (AGEs) and their precursor dicarbonyls are generally perceived as having adverse health effects. They are also considered to be initiators and promoters of disease and aging. However, proof for a causal relationship is ... ...

    Abstract Advanced glycation endproducts (AGEs) and their precursor dicarbonyls are generally perceived as having adverse health effects. They are also considered to be initiators and promoters of disease and aging. However, proof for a causal relationship is lacking. On the other hand, it is known that AGEs and melanoidins possess beneficial properties, such as antioxidant and metal-chelating activities. Furthermore, some AGEs may stimulate the cellular detoxification system, generally known as the phase II drug metabolizing system. We show here that several reactive dicarbonyl intermediates have the capability to stimulate the cellular phase II detoxification systems in both a reporter cell line and primary rat hepatocytes. In addition, we demonstrate that dicarbonyls can attenuate the inflammatory signaling induced by tumor necrosis factor-alpha in a reporter cell system.
    MeSH term(s) Animals ; Anti-Inflammatory Agents/pharmacology ; Cell Line ; Cells, Cultured ; Gene Expression Regulation ; Genes, Reporter ; Glycation End Products, Advanced/pharmacology ; Hepatocytes/cytology ; Hepatocytes/drug effects ; Hepatocytes/physiology ; Hydroquinones/pharmacology ; Polymerase Chain Reaction ; RNA/genetics ; RNA, Messenger/genetics ; Rats ; TATA-Box Binding Protein/genetics
    Chemical Substances Anti-Inflammatory Agents ; Glycation End Products, Advanced ; Hydroquinones ; RNA, Messenger ; TATA-Box Binding Protein ; RNA (63231-63-0) ; 2-tert-butylhydroquinone (C12674942B)
    Language English
    Publishing date 2008-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1196/annals.1433.036
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Glycolaldehyde-modified β-lactoglobulin AGEs are unable to stimulate inflammatory signaling pathways in RAGE-expressing human cell lines

    Buetler, Timo M / Latado, Hélia / Leclerc, Estelle / Weigle, Bernd / Baumeyer, Alexandra / Heizmann, Claus W / Scholz, Gabriele

    Molecular nutrition & food research. 2011 Feb., v. 55, no. 2

    2011  

    Abstract: Scope: Advanced glycation endproducts (AGEs) are suspected to stimulate inflammatory signaling pathways in target tissues via activation of the receptor for AGEs. Endotoxins are generally recognized as potential contamination of AGE preparations and ... ...

    Abstract Scope: Advanced glycation endproducts (AGEs) are suspected to stimulate inflammatory signaling pathways in target tissues via activation of the receptor for AGEs. Endotoxins are generally recognized as potential contamination of AGE preparations and stimulate biological actions that are very similar as or identical to those induced by AGEs. Methods and results: In our study, we used glycolaldehyde-modified β-lactoglobulin preparations as model AGEs and employed two methods to remove endotoxin using either affinity columns or extraction with Triton X-114 (TX-114). Affinity column-purified AGEs retained their ability to stimulate inflammatory signaling as measured by mRNA expression of inflammatory cytokines in the human lung epithelial cell line Beas2b. However, glycolaldehyde-modified AGEs purified by extraction with TX-114 did not show any stimulation of mRNA expression of inflammatory cytokines. The presence of a cell stimulating endotoxin-like activity was demonstrated in the detergent phase after extraction with TX-114, thus indicating that not AGEs but a lipophilic contamination was responsible for the stimulation of inflammatory signaling. Conclusion: Our results demonstrate that glycolaldehyde-modified AGEs are unable to induce inflammatory signaling in receptor for AGE-expressing cells. The observed cell-activating activity can be ascribed to an endotoxin-like lipophilic contamination present in AGE preparations and affinity column purification was insufficient to remove this contamination.
    Keywords cytokines ; endotoxins ; epithelial cells ; gene expression ; glycation ; human cell lines ; humans ; lungs ; messenger RNA ; receptors
    Language English
    Dates of publication 2011-02
    Size p. 291-299.
    Publishing place Wiley-VCH Verlag
    Document type Article
    ZDB-ID 2160372-8
    ISSN 1613-4133 ; 1613-4125
    ISSN (online) 1613-4133
    ISSN 1613-4125
    DOI 10.1002/mnfr.201000140
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Glycolaldehyde-modified β-lactoglobulin AGEs are unable to stimulate inflammatory signaling pathways in RAGE-expressing human cell lines.

    Buetler, Timo M / Latado, Hélia / Leclerc, Estelle / Weigle, Bernd / Baumeyer, Alexandra / Heizmann, Claus W / Scholz, Gabriele

    Molecular nutrition & food research

    2011  Volume 55, Issue 2, Page(s) 291–299

    Abstract: Scope: Advanced glycation endproducts (AGEs) are suspected to stimulate inflammatory signaling pathways in target tissues via activation of the receptor for AGEs. Endotoxins are generally recognized as potential contamination of AGE preparations and ... ...

    Abstract Scope: Advanced glycation endproducts (AGEs) are suspected to stimulate inflammatory signaling pathways in target tissues via activation of the receptor for AGEs. Endotoxins are generally recognized as potential contamination of AGE preparations and stimulate biological actions that are very similar as or identical to those induced by AGEs.
    Methods and results: In our study, we used glycolaldehyde-modified β-lactoglobulin preparations as model AGEs and employed two methods to remove endotoxin using either affinity columns or extraction with Triton X-114 (TX-114). Affinity column-purified AGEs retained their ability to stimulate inflammatory signaling as measured by mRNA expression of inflammatory cytokines in the human lung epithelial cell line Beas2b. However, glycolaldehyde-modified AGEs purified by extraction with TX-114 did not show any stimulation of mRNA expression of inflammatory cytokines. The presence of a cell stimulating endotoxin-like activity was demonstrated in the detergent phase after extraction with TX-114, thus indicating that not AGEs but a lipophilic contamination was responsible for the stimulation of inflammatory signaling.
    Conclusion: Our results demonstrate that glycolaldehyde-modified AGEs are unable to induce inflammatory signaling in receptor for AGE-expressing cells. The observed cell-activating activity can be ascribed to an endotoxin-like lipophilic contamination present in AGE preparations and affinity column purification was insufficient to remove this contamination.
    MeSH term(s) Acetaldehyde/analogs & derivatives ; Acetaldehyde/chemistry ; Cell Line ; Cytokines/genetics ; Cytokines/metabolism ; Detergents/chemistry ; Endotoxins/isolation & purification ; Endotoxins/pharmacology ; Glycation End Products, Advanced/chemistry ; Glycation End Products, Advanced/isolation & purification ; Glycation End Products, Advanced/metabolism ; Humans ; Inflammation/metabolism ; Lactoglobulins/chemistry ; Lactoglobulins/isolation & purification ; Lactoglobulins/metabolism ; Polyethylene Glycols/chemistry ; RNA, Messenger/metabolism ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic/metabolism ; Reproducibility of Results ; Signal Transduction
    Chemical Substances Cytokines ; Detergents ; Endotoxins ; Glycation End Products, Advanced ; Lactoglobulins ; RNA, Messenger ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; Polyethylene Glycols (30IQX730WE) ; Nonidet P-40 (9036-19-5) ; Acetaldehyde (GO1N1ZPR3B) ; glycolaldehyde (W0A0XPU08U)
    Language English
    Publishing date 2011-02
    Publishing country Germany
    Document type Comparative Study ; Journal Article
    ZDB-ID 2160372-8
    ISSN 1613-4133 ; 1613-4125
    ISSN (online) 1613-4133
    ISSN 1613-4125
    DOI 10.1002/mnfr.201000140
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Supplementation with oral probiotic bacteria maintains cutaneous immune homeostasis after UV exposure.

    Guéniche, Audrey / Benyacoub, Jalil / Buetler, Timo M / Smola, Hans / Blum, Stephanie

    European journal of dermatology : EJD

    2006  Volume 16, Issue 5, Page(s) 511–517

    Abstract: Probiotic bacteria have been shown to modulate the immune system of the gut and protect against infectious and inflammatory diseases of the gastro-intestinal tract. Ultraviolet radiation (UVR) is known to alter the cutaneous and systemic immune systems ... ...

    Abstract Probiotic bacteria have been shown to modulate the immune system of the gut and protect against infectious and inflammatory diseases of the gastro-intestinal tract. Ultraviolet radiation (UVR) is known to alter the cutaneous and systemic immune systems implicated in the development of skin tumors. In this study we investigated whether oral probiotics are able to modulate the immune system of the skin using hairless Skh:hr1 mice exposed to an acute dose of UVR. We show that nutritional supplementation with Lactobacillus johnsonii (La1) at 10(8) cfu/day for 10 days was able to protect against the UVR-induced suppression of contact hypersensitivity, the decreased epidermal Langerhans cell density and the increased IL-10 serum levels. In the absence of UV exposure, probiotic bacteria had no detectable effect on the immune system of the skin, thus acting only to re-establish skin homeostasis. In conclusion, our data demonstrate that ingested probiotic bacteria can maintain cutaneous immune capacity after UV exposure.
    MeSH term(s) Animals ; Dermatitis, Contact/immunology ; Female ; Homeostasis/drug effects ; Homeostasis/radiation effects ; Immunity, Innate/drug effects ; Immunity, Innate/radiation effects ; Inflammation/physiopathology ; Interleukin-10/blood ; Lactobacillus ; Langerhans Cells/physiology ; Mice ; Mice, Hairless ; Mice, Inbred Strains ; Probiotics/therapeutic use ; Skin Physiological Phenomena/drug effects ; Skin Physiological Phenomena/radiation effects ; Ultraviolet Rays
    Chemical Substances Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2006-09
    Publishing country France
    Document type Journal Article
    ZDB-ID 1128666-0
    ISSN 1952-4013 ; 1167-1122
    ISSN (online) 1952-4013
    ISSN 1167-1122
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Cyclosporin A generates superoxide in smooth muscle cells.

    Krauskopf, Alexandra / Lhote, Philippe / Petermann, Olivier / Ruegg, Urs T / Buetler, Timo M

    Free radical research

    2005  Volume 39, Issue 9, Page(s) 913–919

    Abstract: Cyclosporin A (CsA) generates superoxide in smooth muscle cells. Our earlier studies have demonstrated that the increase in the vasopressin type 1 receptor induced in vascular smooth muscle cells in the presence of CsA is probably due to superoxide ( ... ...

    Abstract Cyclosporin A (CsA) generates superoxide in smooth muscle cells. Our earlier studies have demonstrated that the increase in the vasopressin type 1 receptor induced in vascular smooth muscle cells in the presence of CsA is probably due to superoxide (Krauskopf et al., J Biol Chem 278, 41685-41690, 2003). This increase in vasopressin receptor is likely at the base of increased vascular responsiveness to vasoconstrictor hormones and hypertension induced by CsA. Here, we demonstrate that CsA produces superoxide. In addition, our data show that superoxide generation does not originate from the major cellular superoxide generating systems NAD(P)H oxidase or xanthine oxidase. Our results suggest that the side effects of CsA could be diminished with the help of SOD mimetic drugs.
    MeSH term(s) Animals ; Aorta/drug effects ; Cells, Cultured ; Cyclosporine/pharmacology ; Dose-Response Relationship, Drug ; Ethidium/analogs & derivatives ; Fluoresceins ; Free Radical Scavengers/pharmacology ; Immunosuppressive Agents/pharmacology ; Male ; Myocytes, Smooth Muscle/drug effects ; Myocytes, Smooth Muscle/metabolism ; Rats ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/antagonists & inhibitors ; Superoxide Dismutase/genetics ; Superoxides/metabolism
    Chemical Substances Fluoresceins ; Free Radical Scavengers ; Immunosuppressive Agents ; Reactive Oxygen Species ; dihydroethidium (104821-25-2) ; Superoxides (11062-77-4) ; diacetyldichlorofluorescein (2044-85-1) ; Cyclosporine (83HN0GTJ6D) ; Superoxide Dismutase (EC 1.15.1.1) ; Ethidium (EN464416SI)
    Language English
    Publishing date 2005-09
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1194130-3
    ISSN 1029-2470 ; 1071-5762
    ISSN (online) 1029-2470
    ISSN 1071-5762
    DOI 10.1080/10715760500104009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.

    Bal-Price, Anna / Crofton, Kevin M / Leist, Marcel / Allen, Sandra / Arand, Michael / Buetler, Timo / Delrue, Nathalie / FitzGerald, Rex E / Hartung, Thomas / Heinonen, Tuula / Hogberg, Helena / Bennekou, Susanne Hougaard / Lichtensteiger, Walter / Oggier, Daniela / Paparella, Martin / Axelstad, Marta / Piersma, Aldert / Rached, Eva / Schilter, Benoît /
    Schmuck, Gabriele / Stoppini, Luc / Tongiorgi, Enrico / Tiramani, Manuela / Monnet-Tschudi, Florianne / Wilks, Martin F / Ylikomi, Timo / Fritsche, Ellen

    Archives of toxicology

    2015  Volume 89, Issue 2, Page(s) 269–287

    Abstract: A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. ...

    Abstract A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.
    MeSH term(s) Brain/drug effects ; Fetus/drug effects ; Guidelines as Topic ; Humans ; Neurotoxicity Syndromes/etiology ; Risk Assessment ; Toxicity Tests/methods
    Language English
    Publishing date 2015-02
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 124992-7
    ISSN 1432-0738 ; 0340-5761
    ISSN (online) 1432-0738
    ISSN 0340-5761
    DOI 10.1007/s00204-015-1464-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Vasopressin type 1A receptor up-regulation by cyclosporin A in vascular smooth muscle cells is mediated by superoxide.

    Krauskopf, Alexandra / Lhote, Philippe / Mutter, Manfred / Dufour, Jean-François / Ruegg, Urs T / Buetler, Timo M

    The Journal of biological chemistry

    2003  Volume 278, Issue 43, Page(s) 41685–41690

    Abstract: Based on our previous results, we investigated whether cyclosporin A (CsA)-induced vasopressin type 1A receptor up-regulation was mediated by free radicals. We report that CsA analogues with different affinities for cyclophilin and calcineurin were able ... ...

    Abstract Based on our previous results, we investigated whether cyclosporin A (CsA)-induced vasopressin type 1A receptor up-regulation was mediated by free radicals. We report that CsA analogues with different affinities for cyclophilin and calcineurin were able to up-regulate vasopressin type 1A receptor and to generate free radicals in smooth muscle cells independently of calcineurin. Further, we demonstrate that the antioxidant N-acetyl-L-cysteine blocked the increase in vasopressin type 1A receptor mRNA and protein levels induced by CsA and that low concentrations of prooxidants were able to directly increase vasopressin type 1A receptor mRNA and protein levels. In addition, short exposure to CsA or pro-oxidants was sufficient to significantly increase vasopressin type 1A receptor mRNA and protein levels. Using cell-permeable forms of superoxide dismutase and catalase, we finally show that superoxide mediates the CsA-induced effects on vasopressin type 1A receptor. These results provide strong evidence that CsA-induced superoxide generation is causally involved in vasopressin type 1A receptor expression and demonstrate for the first time that low physiological concentrations of radicals, most probably superoxide, are able to directly affect cellular signaling to increase vasopressin type 1A receptor expression in rat aortic smooth muscle cells.
    MeSH term(s) Animals ; Aorta/cytology ; Calcineurin/pharmacology ; Catalase/metabolism ; Cyclophilins/pharmacology ; Cyclosporine/pharmacology ; Free Radicals/metabolism ; Male ; Muscle, Smooth, Vascular/cytology ; RNA, Messenger/biosynthesis ; RNA, Messenger/drug effects ; Rats ; Rats, Wistar ; Receptors, Vasopressin/biosynthesis ; Superoxide Dismutase/metabolism ; Superoxides/metabolism ; Superoxides/pharmacology ; Up-Regulation/drug effects
    Chemical Substances Free Radicals ; RNA, Messenger ; Receptors, Vasopressin ; Superoxides (11062-77-4) ; Cyclosporine (83HN0GTJ6D) ; Catalase (EC 1.11.1.6) ; Superoxide Dismutase (EC 1.15.1.1) ; Calcineurin (EC 3.1.3.16) ; Cyclophilins (EC 5.2.1.-)
    Language English
    Publishing date 2003-08-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M301181200
    Database MEDical Literature Analysis and Retrieval System OnLINE

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