témavezető: Nagy Péter
helyszín (magyar oldal): PTE ÁOK Pécs, Szigeti u. 12. helyszín rövidítés: ÁOK
A kutatási téma leírása:
Reactive oxygen species (ROS) are a chemical class of molecules that have generally been considered as deleterious entities because in higher quantities they can damage cellular macromolecules contributing to chronic conditions, such as the emergence of cancer. Therefore, cells have an arsenal of small molecule antioxidants and antioxidant enzymes to protect themselves from oxidative damage. A paradigm shift in the field was introduced by the discovery of the NADPH-oxidases (NOX enzymes), which are dedicated to produce ROS in a variety of cells and tissues. This raised the question whether cells actually need ROS for their normal functions, and if they do, in which processes could they be useful. Today it is generally accepted that ROS indeed play pivotal roles in a variety of cellular functions including defense against invading pathogens or regulation of signal transduction or metabolic pathways. Hence it is now widely accepted that for healthy cellular physiology a delicate redox balance is required.
Reactive cysteine residues represent the primary targets of ROS. In thiol proteins, redox reactions of functional Cys residues at the active site represent the underlying molecular mechanisms of their functions. In other proteins oxidation/reduction of distant regulatory Cys residues can lead to the alteration of protein functions, protein-protein interactions, subcellular localizations or transcriptional regulations. Hydrogen-peroxide (H2O2) has emerged as the major oxidizing agent in redox-signaling events by triggering the reversible oxidation of redox-regulated proteins, including phosphatases, kinases and transcription factors. In recent years it has been shown that the Peroxiredoxin family of proteins serve as central hubs in redox signaling by scavenging >95% of endogenous H2O2 and transducing the redox signal by relaying H2O2-derived oxidizing equivalents on to other proteins.
In addition, we and others have demonstrated that enzyme-regulated endogenous persulfidation events, which are novel oxidative Cys modifications, are highly prevalent in cellular systems playing vital roles in a variety of cellular functions. These discoveries introduced the Reactive Sulfur Species (RSS) concept to redox biology, which is now one of the most heavily investigated direction in the field.
Importantly, an altered redox/persulfidation status have been observed in different cancers. Furthermore, redox regulation and redox signaling as well as sulfane sulfur species play key roles in tumorigenesis and the response to cancer therapeutics. Therefore, our research group is focused on how an altered ROS- and/or RSS-status in cancer cells can reprogram signaling or metabolic events, with the aim to discover novel cancer therapies.
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