Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia-Inducible Factor-1α upon LPS Activation in the Presence of Ample Oxygen.

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autorinnen und Autoren: Siegert I, Schoedel J, Nairz M, Schatz V, Dettmer K, Dick C, Kalucka J, Franke K, Ehrenschwender M, Schley G, Beneke A, Sutter J, Moll M, Hellerbrand C, Wielockx B, Katschinski DM, Lang R, Galy B, Hentze MW, Koivunen P, Oefner PJ, Bogdan C, Weiss G, Willam C, Jantsch J
Zeitschrift: Cell Reports
Verlag: Cell Press
Jahr der Veröffentlichung: 2015
Band: 13
Seitenbereich: 2048 - 2055
ISSN: 2211-1247


Abstract

Both hypoxic and inflammatory conditions activate transcription factors such as hypoxia-inducible factor (HIF)-1α and nuclear factor (NF)-κB, which play a crucial role in adaptive responses to these challenges. In dendritic cells (DC), lipopolysaccharide (LPS)-induced HIF1α accumulation requires NF-κB signaling and promotes inflammatory DC function. The mechanisms that drive LPS-induced HIF1α accumulation under normoxia are unclear. Here, we demonstrate that LPS inhibits prolyl hydroxylase domain enzyme (PHD) activity and thereby blocks HIF1α degradation. Of note, LPS-induced PHD inhibition was neither due to cosubstrate depletion (oxygen or α-ketoglutarate) nor due to increased levels of reactive oxygen species, fumarate, and succinate. Instead, LPS inhibited PHD activity through NF-κB-mediated induction of the iron storage protein ferritin and subsequent decrease of intracellular available iron, a critical cofactor of PHD. Thus, hypoxia and LPS both induce HIF1α accumulation via PHD inhibition but deploy distinct molecular mechanisms (lack of cosubstrate oxygen versus deprivation of co-factor iron).


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Bogdan, Christian Prof. Dr.
Lehrstuhl für Mikrobiologie und Infektionsimmunologie
Lang, Roland Prof. Dr.
Professur für Angeborene Immunität und Pathogenerkennung
Moll, Matthias Dr.
Lehrstuhl für Anorganische und Allgemeine Chemie
Sutter, Jörg Dr.
Lehrstuhl für Anorganische und Allgemeine Chemie
Willam, Carsten Prof. Dr.
Medizinische Klinik 4 - Nephrologie und Hypertensiologie


Einrichtungen weiterer Autorinnen und Autoren

Deutsches Krebsforschungszentrum (DKFZ)
European Molecular Biology Laboratory (EMBL)
Georg-August-Universität Göttingen
Medizinische Universität Innsbruck
Oulun Yliopisto / University of Oulo
Technische Universität Dresden
Universität Regensburg
Universitätsklinikum Regensburg


Zitierweisen

APA:
Siegert, I., Schoedel, J., Nairz, M., Schatz, V., Dettmer, K., Dick, C.,... Jantsch, J. (2015). Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia-Inducible Factor-1α upon LPS Activation in the Presence of Ample Oxygen. Cell Reports, 13, 2048 - 2055. https://dx.doi.org/10.1016/j.celrep.2015.11.005

MLA:
Siegert, Isabel, et al. "Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia-Inducible Factor-1α upon LPS Activation in the Presence of Ample Oxygen." Cell Reports 13 (2015): 2048 - 2055.

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Zuletzt aktualisiert 2019-11-04 um 13:32