Mechanisms and pharmacological interventions in the myocardium and melanoma: “oncocardiology”

Debreceni Egyetem

Gyógyszerészeti Tudományok Doktori Iskola

Tósaki Árpád

gyógyszerészeti tudományok

The aims of the project are to study the changes of necrotic, apoptotic and autophagic cell deaths in connection with the use of pharmacological intervention, including the effects of H2S releasing molecules focusing on myocardial function in ischemic/reperfused (I/R) myocardium obtained from diabetic and nondiabetic rats. Different apoptotic (e.g., beclines) and autophagy-related proteins including LC3II, Beclin-1, Atg-5, Atg-7, and Atg-12 and micro RNA expression will be investigated in spontaneously beating isolated hearts and melanoma cell lines. The research aim expects substantial differences in autophagic/apoptotic signal transduction mechanisms between the nondiabetic and diabetic myocardium. Experiments will be carried out to understand the mechanisms of arrhythmogenesis in connection with various gene/protein expressions related to cell deaths. These experiments may have significant impact to understand whether there is or no any difference in various cell deaths (e.g., necrotic, apoptotic and autophagic deaths) in ischemic/reperfused myocardium in order to avoid sudden cardiac death. Cardiac function (heart rate, coronary flow), infarct size (TTC staining), and H2S release originated from H2S releasing molecules will be registered and measured in the effluent of coronary flow. Cellular toxicity also will be detected in H2C9 cell line. Moreover, the incidence of reperfusion-induced ventricular arrhythmias including ventricular fibrillation, responsible for sudden cardiac death, will be also detected in untreated drug-free and treated myocardium. Additionally, the candidate will focus on pharmacological interventions in various melanoma cell lines in connection with the mechanisms of autophagic, necrotic, and apoptotic processes.

Pharm

2025-05-15

English B2 level