RESEARCH GROUP LEADER: Prof. Dr. Péter NAGY, PhD, DSc
CONTACT: [Click to see email]
MEMBERS:
1) Prof. Edward E. SCHMIDT, PhD
2) Dr. Dóra KŐVÁRI, PhD
3) Dr. Vivien CSIKÓS-KISS, PhD
4) Noémi BADARI
RESEARCH TOPIC:
Maintaining redox homeostasis is a primary goal for all living cells. The two key players of reducing capacity in mammalian cells are the NADPH-dependent thioredoxin reductase and glutathione reductase, which control basic cellular functions. Our mouse modell has liver cells lacking both key enzymes (TR/GR-null ) simultaneously. According to our hypothesis, cysteine persulfide (Cys-SSH) provides the missing reducing power, formed by PLP-dependent transsulfuration enzymes (CBS, CSE) using extracellular cistine, capable of neutralizing accumulated oxidants in multiple steps and – in the lack of disulfide reductase systems – maintaining the otherwise impaired Cys supply, which is essential in protein and GSH synthesis. Throughout our research, we assess the contribution of Cys-SSH formation to antioxidant protection and cysteine replacement; compare the importance of cystine and Met-based transsulfuration pathways in the WT and TR/GR-null liver, and follow the metabolic flux of sulfur-containing amino acids. In the course of the project we expect to gain comprehensive knowledge regarding the regulation of transsulfuration metabolic pathways and the roles played by enzymes in protection against oxidative stress, which, based on our previous research, are of utmost importance in developing new therapeutic approaches for cancer.
TOP PUBLICATIONS:
1) Katalin Erdélyi, … Péter Nagy, 2021, PNAS, Reprogrammed Transsulfuration Promotes Basal Like Breast Tumor Progression via Realigning Cellular Cysteine-Persulfidation
2) Ágnes Czikora, …, Péter Nagy, 2022, Redox Biology, Cystathionine β-Synthase Overexpression Drives Metastatic Dissemination in Pancreatic Ductal Adenocarcinoma via Inducing Epithelial-to-Mesenchymal Transformation of Cancer Cells
3) Viktor Kožich, …, Péter Nagy, 2022, Redox Biology, Human ultrarare genetic disorders of sulfur metabolism demonstrate redundancies in H2S homeostasis
4) Éva Dóka, …, Péter Nagy, 2021, Sci Adv, Comment on “Evidence that the ProPerDP method is inadequate for protein persulfidation detection due to lack of specificity”
5) Tamás Gálla, Péter Nagy,…, József Balla, 2022, Redox Biology, Overview on hydrogen sulfide-mediated suppression of vascular calcification and hemoglobin/heme-mediated vascular damage in atherosclerosis
GRANT PROJECTS:
1) Understanding and targeting redox systems in a preclinical liver cancer model
2) Sulfur Metabolism Under Stress