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4 results on '"SWINKELS, Dorine W."'

1. Inhibition of Nrf2 alters cell stress induced by chronic iron exposure in human proximal tubular epithelial cells

Author

van Raaij, S E G, Masereeuw, R, Swinkels, Dorine W., van Swelm, Rachel P L, Afd Pharmacology, Pharmacology, Afd Pharmacology, and Pharmacology

Subjects
0301 basic medicine, medicine.medical_specialty, Antioxidant, Time Factors, NF-E2-Related Factor 2, medicine.medical_treatment, Toxicology, medicine.disease_cause, Ferric Compounds, Renal proximal tubular epithelial cell, Nrf2, Cell Line, Kidney Tubules, Proximal, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Alkaloids, All institutes and research themes of the Radboud University Medical Center, Trigonelline, Internal medicine, medicine, NAD(P)H Dehydrogenase (Quinone), Humans, Iron overload, chemistry.chemical_classification, Reactive oxygen species, biology, Dose-Response Relationship, Drug, General Medicine, Ferritin, Heme oxygenase, Cytosol, 030104 developmental biology, Endocrinology, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], chemistry, Oxidative stress, 030220 oncology & carcinogenesis, Ferritins, biology.protein, Unfolded protein response, Kidney Diseases, Reactive Oxygen Species, ER stress, Heme Oxygenase-1, Transcription Factor CHOP, Signal Transduction
Abstract

Iron can catalyze reactive oxygen species (ROS) formation, causing cellular injury. In systemic iron overload, renal tubular epithelial cells are luminally exposed to high iron levels due to glomerular filtration of increased circulating iron. Reports of tubular dysfunction and iron deposition in β-thalassemia major support an association between increased chronic iron exposure and renal tubular injury. In acute iron exposure, Nuclear factor-erythroid 2-related factor 2 (Nrf2) may protect from iron-induced injury, whereas chronic renal stress may lead to Nrf2 exhaustion. We studied the cytotoxic mechanisms of chronic iron exposure using human conditionally immortalized proximal tubular epithelial cells (ciPTECs). Long-term iron exposure resulted in iron accumulation, cytosolic ROS formation and increased heme oxygenase 1 (HMOX-1) mRNA expression (all p

Published
2018

2. Iron-Induced Virulence of Salmonella enterica Serovar Typhimurium at the Intestinal Epithelial Interface Can Be Suppressed by Carvacrol

Author

Kortman, Guus A M, Roelofs, Rian W H M, Swinkels, Dorine W., De Jonge, Marien I., Burt, Sara A., Tjalsma, Harold, Faculty of Veterinary Medicine Research Groups, LS IRAS VPH VV (veterinaire volksgezh.), Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA2, Faculty of Veterinary Medicine Research Groups, LS IRAS VPH VV (veterinaire volksgezh.), Risk Assessment of Toxic and Immunomodulatory Agents, and IRAS RATIA2

Subjects
Salmonella typhimurium, Salmonella, Iron, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Virulence, Microbial Sensitivity Tests, medicine.disease_cause, Ferric Compounds, Bacterial Adhesion, Microbiology, chemistry.chemical_compound, Intestinal mucosa, Taverne, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], medicine, Humans, Pharmacology (medical), Carvacrol, Intestinal Mucosa, Mechanisms of Action: Physiological Effects, Pharmacology, chemistry.chemical_classification, Dose-Response Relationship, Drug, biology, Antimicrobial, biology.organism_classification, Anti-Bacterial Agents, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Infectious Diseases, chemistry, Caco-2, Transferrin, Salmonella enterica, Monoterpenes, Cymenes, Caco-2 Cells
Abstract

Oral iron therapy can increase the abundance of bacterial pathogens, e.g., Salmonella spp., in the large intestine of African children. Carvacrol is a natural compound with antimicrobial activity against various intestinal bacterial pathogens, among which is the highly prevalent Salmonella enterica serovar Typhimurium. This study aimed to explore a presumed interaction between carvacrol and bacterial iron handling and to assess the potential of carvacrol in preventing the increase of bacterial pathogenicity during high iron availability. S . Typhimurium was cultured with increasing concentrations of iron and carvacrol to study the effects of these combined interventions on growth, adhesion to intestinal epithelial cells, and iron uptake/influx in both bacterial and epithelial cells. In addition, the ability of carvacrol to remove iron from the high-affinity ligand transferrin and an Fe-dye complex was examined. Carvacrol retarded growth of S . Typhimurium at all iron conditions. Furthermore, iron-induced epithelial adhesion was effectively reduced by carvacrol at high iron concentrations. The reduction of growth and virulence by carvacrol was not paralleled by a change in iron uptake or influx into S . Typhimurium. In contrast, bioavailability of iron for epithelial cells was moderately decreased under these conditions. Further, carvacrol was shown to lack the properties of an iron binding molecule; however, it was able to weaken iron-ligand interactions by which it may possibly interfere with bacterial virulence. In conclusion, our in vitro data suggest that carvacrol has the potential to serve as a novel dietary supplement to prevent pathogenic overgrowth and colonization in the large intestine during oral iron therapy.

Published
2014

3. Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Author

Benyamin, Beben, Esko, Tonu, Ried, Janina S, Radhakrishnan, Aparna, Vermeulen, Sita H, Traglia, Michela, Gögele, Martin, Anderson, Denise, Broer, Linda, Podmore, Clara, Luan, Jian'An, Kutalik, Zoltan, Sanna, Serena, van der Meer, Peter, Tanaka, Toshiko, Wang, Fudi, Westra, Harm Jan, Franke, Lude, Mihailov, Evelin, Milani, Lili, Hälldin, Jonas, Häldin, Jonas, Winkelmann, Juliane, Meitinger, Thomas, Thiery, Joachim, Peters, Annette, Waldenberger, Melanie, Rendon, Augusto, Jolley, Jennifer, Sambrook, Jennifer, Kiemeney, Lambertus A, Sweep, Fred C, Sala, Cinzia F, Schwienbacher, Christine, Pichler, Irene, Hui, Jennie, Demirkan, Ayse, Isaacs, Aaron, Amin, Najaf, Steri, Maristella, Waeber, Gérard, Verweij, Niek, Powell, Joseph E, Nyholt, Dale R, Heath, Andrew C, Madden, Pamela A. F, Visscher, Peter M, Wright, Margaret J, Montgomery, Grant W, Martin, Nicholas G, Hernandez, Dena, Bandinelli, Stefania, van der Harst, Pim, Uda, Manuela, Vollenweider, Peter, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, van Duijn, Cornelia, Beilby, John, Pramstaller, Peter P, Hicks, Andrew A, Ouwehand, Willem H, Oexle, Konrad, Gieger, Christian, Metspalu, Andres, Camaschella, Clara, Toniolo, Daniela, Swinkels, Dorine W, Whitfield, John B., PANICO, SALVATORE, Podmore, Clara [0000-0002-2452-8067], Luan, Jian'an [0000-0003-3137-6337], Rendon Restrepo, Augusto [0000-0001-8994-0039], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Ouwehand, Willem [0000-0002-7744-1790], Apollo - University of Cambridge Repository, Benyamin, Beben, Esko, Tonu, Ried, Janina S, Radhakrishnan, Aparna, Vermeulen, Sita H, Traglia, Michela, Gögele, Martin, Anderson, Denise, Broer, Linda, Podmore, Clara, Luan, Jian'An, Kutalik, Zoltan, Sanna, Serena, van der Meer, Peter, Tanaka, Toshiko, Wang, Fudi, Westra, Harm Jan, Franke, Lude, Mihailov, Evelin, Milani, Lili, Hälldin, Jona, Häldin, Jona, Winkelmann, Juliane, Meitinger, Thoma, Thiery, Joachim, Peters, Annette, Waldenberger, Melanie, Rendon, Augusto, Jolley, Jennifer, Sambrook, Jennifer, Kiemeney, Lambertus A, Sweep, Fred C, Sala, Cinzia F, Schwienbacher, Christine, Pichler, Irene, Hui, Jennie, Demirkan, Ayse, Isaacs, Aaron, Amin, Najaf, Steri, Maristella, Waeber, Gérard, Verweij, Niek, Powell, Joseph E, Nyholt, Dale R, Heath, Andrew C, Madden, Pamela A. F, Visscher, Peter M, Wright, Margaret J, Montgomery, Grant W, Martin, Nicholas G, Hernandez, Dena, Bandinelli, Stefania, van der Harst, Pim, Uda, Manuela, Vollenweider, Peter, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, van Duijn, Cornelia, Beilby, John, Pramstaller, Peter P, Hicks, Andrew A, Ouwehand, Willem H, Oexle, Konrad, Gieger, Christian, Metspalu, Andre, Camaschella, Clara, Toniolo, Daniela, Swinkels, Dorine W, Whitfield, John B., Panico, Salvatore, Internal Medicine, Epidemiology, Erasmus MC other, Benyamin, B, Esko, T, Ried, J, Radhakrishnan, A, Vermeulen, Sh, Traglia, M, Gogele, M, Anderson, D, Broer, L, Podmore, C, Luan, J, Kutalik, Z, Sanna, S, VAN DER MEER, P, Tanaka, T, Wang, F, Westra, Hj, Franke, L, Mihailov, E, Milani, L, Haldin, J, Winkelmann, J, Meitinger, T, Thiery, J., Cardiovascular Centre (CVC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), InterAct Consortium, and Whitfield, John B

Subjects
FERRITIN LEVELS, General Physics and Astronomy, Transferrin/metabolism, Genome-wide association study, 0302 clinical medicine, Chromosomes, Human, Pair 7/genetics, Risk Factors, GENETIC-VARIANTS, Homeostasis, chemistry.chemical_classification, Genetics, TRANSFERRIN RECEPTOR 2, 0303 health sciences, education.field_of_study, Multidisciplinary, HFE HEREDITARY HEMOCHROMATOSIS, Transferrin, COMMON VARIANTS, Lipid, FOAM CELL-FORMATION, Polymorphism, Single Nucleotide/genetics, Lipids, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, ARNTL, Phenotype, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, CORONARY-ARTERY-DISEASE, Hemochromatosis, HFE Protein, Single Nucleotide/genetics, Chromosomes, Human, Pair 7, Human, Adult, Hemochromatosi, Iron, Reproducibility of Result, Transferrin receptor, Single-nucleotide polymorphism, Genetic Association Studie, Biology, Polymorphism, Single Nucleotide, Chromosomes, Article, General Biochemistry, Genetics and Molecular Biology, hemochromatosis, 03 medical and health sciences, Homeostasi, TOTAL MORTALITY, medicine, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, education, Iron/blood, Genetic Association Studies, 030304 developmental biology, Genetic association, Ferritin, Lipids/blood, Risk Factor, CIRCADIAN-RHYTHM, Hemochromatosis/blood, Reproducibility of Results, General Chemistry, Homeostasis/genetics, medicine.disease, Ferritins/metabolism, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Gene Expression Regulation, chemistry, Pair 7/genetics, Genetic Loci, Ferritins, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5]
Abstract

Contains fulltext : 137523.pdf (Publisher’s version ) (Open Access) Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P

Published
2014

4. Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Author

Benyamin, Beben, Esko, Tonu, Ried, Janina S, Radhakrishnan, Aparna, Vermeulen, Sita H, Traglia, Michela, Gögele, Martin, Anderson, Denise, Broer, Linda, Podmore, Clara, Luan, Jian'an, Kutalik, Zoltan, Sanna, Serena, Van Der Meer, Peter, Tanaka, Toshiko, Wang, Fudi, Westra, Harm-Jan, Franke, Lude, Mihailov, Evelin, Milani, Lili, Hälldin, Jonas, Winkelmann, Juliane, Meitinger, Thomas, Thiery, Joachim, Peters, Annette, Waldenberger, Melanie, Rendon, Augusto, Jolley, Jennifer, Sambrook, Jennifer, Kiemeney, Lambertus A, Sweep, Fred C, Sala, Cinzia F, Schwienbacher, Christine, Pichler, Irene, Hui, Jennie, Demirkan, Ayse, Isaacs, Aaron, Amin, Najaf, Steri, Maristella, Waeber, Gérard, Verweij, Niek, Powell, Joseph E, Nyholt, Dale R, Heath, Andrew C, Madden, Pamela AF, Visscher, Peter M, Wright, Margaret J, Montgomery, Grant W, Martin, Nicholas G, Hernandez, Dena, Bandinelli, Stefania, Van Der Harst, Pim, Uda, Manuela, Vollenweider, Peter, Scott, Robert A, Langenberg, Claudia, Wareham, Nicholas J, InterAct Consortium, Van Duijn, Cornelia, Beilby, John, Pramstaller, Peter P, Hicks, Andrew A, Ouwehand, Willem H, Oexle, Konrad, Gieger, Christian, Metspalu, Andres, Camaschella, Clara, Toniolo, Daniela, Swinkels, Dorine W, and Whitfield, John B

Subjects
Adult, Iron, Transferrin, Reproducibility of Results, Lipids, Polymorphism, Single Nucleotide, 3. Good health, Phenotype, Gene Expression Regulation, Genetic Loci, Risk Factors, Ferritins, Homeostasis, Humans, Genetic Predisposition to Disease, Hemochromatosis, Chromosomes, Human, Pair 7, Genetic Association Studies
Abstract

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P

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