Thesis supervisor: Péter Nagy
Location of studies (in Hungarian): PTE ÁOK Pécs, Szigeti u. 12. Abbreviation of location of studies: ÁOK
Description of the research topic:
The medical importance of endogenously produced small signaling molecules is highlighted by the 1998 Nobel Prize in Medicine, which recognized the physiological mediatory role of nitric oxide (NO). The newest member of small signaling agents is hydrogen sulfide, which is generated in vivo during metabolic pathways of cysteine [1] . The field of H2S biology has exploded in the past decade [2], which (as a usual consequence of rapidly growing research areas) entails an increasing number of controversial observations in the literature. Our research group is dedicated to reconcile some of these controversies by studying the underlying molecular mechanisms of sulfide’s biological actions [3, 4].
We are interested in the following three major pathways of sulfide signaling:
1) Orchestrating the functions of thiol proteins and protection against oxidative stress via sulfide-mediated persulfide formation. [5-8]
2) Interactions of sulfide with metalloproteins (coordination vs redox chemistry at the active sites). [7, 9]
3) Cross-talk between NO and sulfide signaling via chemical reactions between NO, sulfide, persulfides and nitroso-thiols [10, 11]
The PhD candidate will undertake a rigorous biochemical investigation of one (or more) of the above pathways.
References
1. Wang, R., Physiological implications of hydrogen sulfide: a whiff exploration that blossomed. Physiological reviews, 2012. 92(2): p. 791-896.
2. Kimura, H., H2S2014 in Kyoto the 3 international conference on HS in biology and medicine. Nitric Oxide, 2014.
3. Nagy, P., Mechanistic Chemical Perspective of Hydrogen Sulfide Signaling. Methods in Enzymology, 2015.
4. Nagy, P., et al., Chemical aspects of hydrogen sulfide measurements in physiological samples. Biochimica et biophysica acta, 2014. 1840(2): p. 876-91.
5. Greiner, R., et al., Polysulfides link H2S to protein thiol oxidation. Antioxidants and Redox Signaling, 2013. 19(15): p. 1749-65.
6. Nagy, P. and C.C. Winterbourn, Rapid reaction of hydrogen sulfide with the neutrophil oxidant hypochlorous acid to generate polysulfides. Chemical Research in Toxicology, 2010. 23(10): p. 1541-3.
7. Ono, K., et al., Redox chemistry and chemical biology of H2S, hydropersulfides, and derived species: implications of their possible biological activity and utility. Free radical biology & medicine, 2014. 77: p. 82-94.
8. Vasas, A., et al., Kinetic and thermodynamic studies on the disulfide-bond reducing potential of hydrogen sulfide. Nitric Oxide, 2014.
9. Palinkas, Z., et al., Interactions of hydrogen sulfide with myeloperoxidase. British journal of pharmacology, 2014.
10. Berenyiova, A., et al., The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants. Nitric Oxide, 2014.
11. Cortese-Krott, M.M., et al., Nitrosopersulfide (SSNO(-)) accounts for sustained NO bioactivity of S-nitrosothiols following reaction with sulfide. Redox biology, 2014. 2: p. 234-44.
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