Project Details
Projekt
Steroid Hormones as Regulators of Ferroptosis Sensitivity During Acute Kidney Injury
Applicant
Professor Dr. Andreas Linkermann
Subject Area
Cell Biology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 460938556
Dexamethasone and other steroid hormones are widely used drugs, the use of which goes beyond the most common applications of autoimmune diseases or the prevention of transplant rejection. Side effects have been known to limit the applicable dosage of steroids, but despite the widespread clinical use, no conclusive mechanism of action has been described to explain the untoward functions. As a continuation of our previous work on the exquisite sensitivity of adrenocortical carcinomas to ferroptosis, we provide preliminary data for steroid hormones to significantly lower the threshold to ferroptosis in established cell culture assays. In addition, we recently found two rodent strains, ferroptosis suppressor protein 1 (FSP1)-deficient and glutathione peroxidase 4 (GPX4)-mutated mice, to exhibit extraordinary sensitivity to ferroptosis induction in mouse models of acute kidney injury (AKI). Here, we propose to combine these two findings to perform a set of work packages which allow testing the central hypothesis of steroid hormone-mediated promotion of ferroptosis. We aim to characterize the ferroptosis promoting effect of steroid hormones in cell lines in more detail and assess ferroptosis regulation by steroid hormones in primary renal tissue. We will finally elucidate the role of steroid hormones on AKI in mice and clarify if FSP1 or GPX4 are directly regulated by steroids, or, alternatively, if yet undefined surveillance systems are involved. This project aligns with the aims and framework of the SPP3206.
DFG Programme
Priority Programmes
Co-Investigator
Dr. Anne von Mäßenhausen
