Publikation: Heme oxygenase 1 protects human colonocytes against ROS formation, oxidative DNA damage and cytotoxicity induced by heme iron, but not inorganic iron
Dateien
Datum
Autor:innen
Herausgeber:innen
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
DOI (zitierfähiger Link)
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Titel in einer weiteren Sprache
Publikationstyp
Publikationsstatus
Erschienen in
Zusammenfassung
The consumption of red meat is probably carcinogenic to humans and is associated with an increased risk to develop colorectal cancer (CRC). Red meat contains high amounts of heme iron, which is thought to play a causal role in tumor formation. In this study, we investigated the genotoxic and cytotoxic effects of heme iron (i.e., hemin) versus inorganic iron in human colonic epithelial cells (HCEC), human CRC cell lines and murine intestinal organoids. Hemin catalyzed the formation of reactive oxygen species (ROS) and induced oxidative DNA damage as well as DNA strand breaks in both HCEC and CRC cells. In contrast, inorganic iron hardly affected ROS levels and only slightly increased DNA damage. Hemin, but not inorganic iron, caused cell death and reduced cell viability. This occurred preferentially in non-malignant HCEC, which was corroborated in intestinal organoids. Both hemin and inorganic iron were taken up into HCEC and CRC cells, however with differential kinetics and efficiency. Hemin caused stabilization and nuclear translocation of Nrf2, which induced heme oxygenase-1 (HO-1) and ferritin heavy chain (FtH). This was not observed after inorganic iron treatment. Chemical inhibition or genetic knockdown of HO-1 potentiated hemin-triggered ROS generation and oxidative DNA damage preferentially in HCEC. Furthermore, HO-1 abrogation strongly augmented the cytotoxic effects of hemin in HCEC, revealing its pivotal function in colonocytes and highlighting the toxicity of free intracellular heme iron. Taken together, this study demonstrated that hemin, but not inorganic iron, induces ROS and DNA damage, resulting in a preferential cytotoxicity in non-malignant intestinal epithelial cells. Importantly, HO-1 conferred protection against the detrimental effects of hemin.
Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
Schlagwörter
Konferenz
Rezension
Zitieren
ISO 690
SEIWERT, Nina, Sabine WECKLEIN, Philipp DEMUTH, Solveig HASSELWANDER, Talke A KEMPER, Tanja SCHWERDTLE, Thomas BRUNNER, Jörg FAHRER, 2020. Heme oxygenase 1 protects human colonocytes against ROS formation, oxidative DNA damage and cytotoxicity induced by heme iron, but not inorganic iron. In: Cell Death and Disease. Nature Publishing Group. 2020, 11(9), 787. eISSN 2041-4889. Available under: doi: 10.1038/s41419-020-02950-8BibTex
@article{Seiwert2020-09-23oxyge-51309, year={2020}, doi={10.1038/s41419-020-02950-8}, title={Heme oxygenase 1 protects human colonocytes against ROS formation, oxidative DNA damage and cytotoxicity induced by heme iron, but not inorganic iron}, number={9}, volume={11}, journal={Cell Death and Disease}, author={Seiwert, Nina and Wecklein, Sabine and Demuth, Philipp and Hasselwander, Solveig and Kemper, Talke A and Schwerdtle, Tanja and Brunner, Thomas and Fahrer, Jörg}, note={Article Number: 787} }
RDF
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/51309"> <dc:contributor>Kemper, Talke A</dc:contributor> <dc:creator>Hasselwander, Solveig</dc:creator> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <dcterms:abstract xml:lang="eng">The consumption of red meat is probably carcinogenic to humans and is associated with an increased risk to develop colorectal cancer (CRC). Red meat contains high amounts of heme iron, which is thought to play a causal role in tumor formation. In this study, we investigated the genotoxic and cytotoxic effects of heme iron (i.e., hemin) versus inorganic iron in human colonic epithelial cells (HCEC), human CRC cell lines and murine intestinal organoids. Hemin catalyzed the formation of reactive oxygen species (ROS) and induced oxidative DNA damage as well as DNA strand breaks in both HCEC and CRC cells. In contrast, inorganic iron hardly affected ROS levels and only slightly increased DNA damage. Hemin, but not inorganic iron, caused cell death and reduced cell viability. This occurred preferentially in non-malignant HCEC, which was corroborated in intestinal organoids. Both hemin and inorganic iron were taken up into HCEC and CRC cells, however with differential kinetics and efficiency. Hemin caused stabilization and nuclear translocation of Nrf2, which induced heme oxygenase-1 (HO-1) and ferritin heavy chain (FtH). This was not observed after inorganic iron treatment. Chemical inhibition or genetic knockdown of HO-1 potentiated hemin-triggered ROS generation and oxidative DNA damage preferentially in HCEC. Furthermore, HO-1 abrogation strongly augmented the cytotoxic effects of hemin in HCEC, revealing its pivotal function in colonocytes and highlighting the toxicity of free intracellular heme iron. Taken together, this study demonstrated that hemin, but not inorganic iron, induces ROS and DNA damage, resulting in a preferential cytotoxicity in non-malignant intestinal epithelial cells. Importantly, HO-1 conferred protection against the detrimental effects of hemin.</dcterms:abstract> <dc:contributor>Fahrer, Jörg</dc:contributor> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/51309"/> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2020-10-12T11:34:23Z</dcterms:available> <dc:creator>Wecklein, Sabine</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/"/> <dc:contributor>Hasselwander, Solveig</dc:contributor> <dc:creator>Demuth, Philipp</dc:creator> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:issued>2020-09-23</dcterms:issued> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/51309/1/Seiwert_2-p5b01823ac5i4.pdf"/> <dc:creator>Schwerdtle, Tanja</dc:creator> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/51309/1/Seiwert_2-p5b01823ac5i4.pdf"/> <dc:contributor>Seiwert, Nina</dc:contributor> <dc:creator>Seiwert, Nina</dc:creator> <dc:contributor>Schwerdtle, Tanja</dc:contributor> <dc:contributor>Wecklein, Sabine</dc:contributor> <dc:creator>Brunner, Thomas</dc:creator> <dc:language>eng</dc:language> <dcterms:title>Heme oxygenase 1 protects human colonocytes against ROS formation, oxidative DNA damage and cytotoxicity induced by heme iron, but not inorganic iron</dcterms:title> <dc:creator>Kemper, Talke A</dc:creator> <dc:contributor>Demuth, Philipp</dc:contributor> <dc:creator>Fahrer, Jörg</dc:creator> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2020-10-12T11:34:23Z</dc:date> <dc:rights>Attribution 4.0 International</dc:rights> <dc:contributor>Brunner, Thomas</dc:contributor> </rdf:Description> </rdf:RDF>