Ina Eisenbach

GT-Posterpreis 2017 für Ina Eisenbach

Oxidative stress is regarded as a major trigger for neuronal dysfunction and death in the ageing brain and in multiple neurodegenerative disorders. How oxidative stress mediates neuronal death and whether the associated mechanisms are accessible for therapeutic intervention strategies is not clarified. Increasing evidence suggests that oxidative stress triggers mechanisms of regulated necrosis that involve the activation of receptor interacting protein 1 (RIP1) independently of death receptor activation.

Recently, we identified a pivotal role for cylindromatosis (CYLD) driving RIP1 activation and necrosome formation in oxidative death pathways in neurons. In a model of glutamate-induced oxidative death (oxytosis) in neuronal HT-22 cells we characterized protective effects of siRNA-mediated CYLD gene silencing which involved inhibition of RIP1/RIP3 complex formation. Additionally, experiments in CYLD-/- mice revealed protection against traumatic brain injury demonstrating an important function of CYLD in acute neuronal injury in vivo. Since oxytosis and ferroptosis share common features in their signaling pathways, like GSH depletion and inhibition of GPX4, increased lipid peroxidation and mitochondrial damage, it was of great interest to investigate a potential role of CYLD in mitochondrial death pathways in paradigms of erastin-induced ferroptosis.

Here, we show in neuronal HT-22 cells that erastin-mediated formation of reactive oxygen species (ROS) triggers mechanisms of regulated necrosis independent of TNFα-signaling. In this model system of ferroptosis, erastin promotes glutathione depletion and lipid peroxidation followed by activation of RIP1 and subsequent RIP1/RIP3 necrosome formation which is regarded as a hallmark of regulated necrosis. Silencing of RIP1 by siRNA or by the RIP1 inhibitor necrostatin-1 prevented erastin-induced cell death. In contrast, the ferroptosis inhibitor ferrostatin-1 failed to protect cells against TNF α-induced classical necroptosis, a form of programmed cell death that is mediated by RIP-kinases downstream of death receptor activation. In further steps, the impact of CYLD was investigated by siRNA-mediated gene silencing or gene knockout via the CRISPR/Cas-9 system, respectively. In erastin-induced ferroptosis, CYLD depletion decreased RIP1/RIP3 complex formation and promoted neuronal survival. Furthermore, we revealed the involvement of mitochondrial fission regulating dynamin-related protein 1 (DRP-1) since genetic depletion or pharmacological inhibition of DRP-1 protected HT-22 cells against erastin toxicity. CYLD knockout prevented erastin-induced DRP-1 translocation to mitochondria as well as mitochondrial ROS production and the loss of mitochondrial membrane potential, suggesting that CYLD and DRP-1 can link mechanisms of regulated necrosis to mitochondrial pathways of cell death in paradigms of oxidative stress

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3rd German Pharm-Tox Summit

Invitation & Call for Abstract

We would like to cordially invite you to take part in this outstanding event by submitting abstracts for oral and poster presentations until 26 October 2017!

Please submit your abstracts in English here.

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The Long-range Research Initiative (LRI) programme of the European Chemical Industry Council (Cefic) is now accepting grant applications to carry out research in different areas.

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Deadline: 31 August 2017

Expertinnen und Experten für das OECD-Prüfrichtlinienprogramm gesucht

Das Bundesinstitut für Risikobewertung sucht Expertinnen und Experten zur Unterstützung des nationalen Koordinators im Bereich Gesundheit für das OECD-Prüfrichtlinienprogramm.

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Sonderheft "Human Biomonitoring 2016" erschienen

Das Sonderheft "Human Biomonitoring 2016", Volume 220/2 Part A der Zeitschrift International Journal of Hygiene and Environmental Health ist erschienen. Insgesamt 34 Beiträge stellen den aktuellen Stand des weltweiten Human-Biomonitorings (HBM) dar.

Das Sonderheft wurde im Nachgang zur 2. Internationalen Human-Biomonitoring Konferenz, Berlin 2016, zusammengestellt, die unter dem Motto "Wissenschaft und Politik für eine gesunde Zukunft" gemeinsam vom Umweltbundesamt und dem Bundesministerium für Umwelt, Naturschutz, Bau und Reaktorsicherheit durchgeführt wurde.

Alle Artikel sind ein Jahr im Open-Access online frei verfügbar: www.sciencedirect.com/...

Poster der GT auf der SOT-Tagung 2017

Society of Toxicology 56th Annual Meeting and ToxExpo, March 12–16, 2017, in Baltimore, Maryland
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Expertinnen und Experten zum Schutz von Versuchstieren gesucht

Der Nationale Ausschuss Tierschutzgesetz (TierSchG) des BfR baut einen ehrenamtlich arbeitenden Expertenpool auf.

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Poster der GT auf der SOT-Tagung 2016

Society of Toxicology 55th Annual Meeting and ToxExpo, March 13–17, 2016, in New Orleans
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Arsen in Lebensmitteln und in Trinkwasser
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Toxikologen warnen: Gesundheits- und Umweltschutz in Gefahr; Fachgesellschaft beklagt Mangel an Ausbildungsplätzen
PDToxGes2015.pdf

Wissenschafltiche Ausarbeitung

Toxikologie in Deutschland 2015
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Positionspapier des Arbeitskreises zum Humanbiomonitoring


Humanbiomonitoring.pdf