Thesis supervisor: Renáta Molnár-Gáspár
Location of studies (in Hungarian): University of Szeged, Departmet ogf Biochemistry, Abbreviation of location of studies: ÁOK
Description of the research topic:
Several biologically active molecules are synthesized from tryptophan through kynurenine pathway. Among them, the kynurenic acid has a neuroprotective effect in different neurodegenerative diseases, where it can reduce the damage of neurons. It exerts primarily its protective effect as an antagonist of ionotropic glutamate receptors and ameliorates the excitotoxic cellular injury. In addition, as an anti-inflammatory agent can moderate the inflammation associated with neurological disorders and as an antioxidant molecule takes part in the elimination of reactive oxygen species-induced oxidative stress. Based on this knowledge, some elements of the kynurenic pathway may become potential neurological drug development targets. Thus, its cardiovascular effects should be thoroughly investigated. However, the physiological and pathological effects - including the molecular mechanisms of action - of tryptophan metabolites on myocardium are unknown. Therefore our goal is to explore and investigate the underlying mechanisms of action. Within the program, we aim to investigate the effect of exogenously administered kynurenic acid on myocardium in stress-free and different stress conditions using in vitro, ex vivo and in vivo experimental systems (for example simulated ischemia/reperfusion, global ischemia model, antitumor drugs-induced cardio-cytotoxicity models). During the exploration of kynurenic acid’s molecular mechanism, we investigate the potential role of mitochondrial function, apoptosis, autophagy and other pathways involved in cardioprotection and stress adaptation.
Methods: in vitro primary cell culture and cell line-based test systems, modeling of acute myocardial infarction, development and use of different cytostatics-induced cardio-cytotoxicity models, biochemical and molecular biological investigation of at the cellular level (fluorescent and colorimetric viability and enzyme activity measurements using of microplate reader, western blot, qRT-PCR), ex vivo Langendorf heart perfusion, in vivo determination of hemodynamic parameters.
Required language skills: Eglish B2 Further requirements: TDK munka
Number of students who can be accepted: 3
Deadline for application: 2021-11-10
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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