Project Details
Projekt
5-Lipoxygenase as immunoregulatory target of human endogenous vitamin E metabolites
Applicant
Professor Dr. Andreas Koeberle
Subject Area
Pharmacy
Term
from 2017 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 378292525
Vitamin E has immunoregulatory functions and protects from metabolic and inflammatory diseases at low dosage. The vitamin has long been viewed as mere antioxidant. Meanwhile, the focus of basic research shifted to non-redox mechanisms, and it has been hypothesized that vitamin E is converted into bioactive metabolites, as known for other fat-soluble vitamins. Our data indicate that the vitamin E metabolite 13'-carboxy-alpha-tocopherol is endogenously formed in the body and contributes to the anti-inflammatory properties of vitamin E through inhibition of 5-lipoxygenase - a key enzyme in the biosynthesis of immunoregulatory lipid mediators. In the present proposal, we will in detail investigate the binding mode and inhibitory mechanism of vitamin E metabolites and characterize 13'-carboxy-alpha-tocopherol as endogenous metabolite in human primary immune cells, in a biochip-based microperfused three-dimensional liver organoid as well as in a mouse model of inflammation. Our results will provide insights into the complex mechanisms of vitamin E and might be of major importance for the design and interpretation of vitamin E supplementation studies.
DFG Programme
Research Grants
International Connection
Austria, France, Italy, USA
