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A Szentágothai János Kutatóközpont a PTE korszerű, nemzetközi tudományszervezési és menedzsment normák szerint kialakított új intézménye, amely az élettudományi, élettelen természettudományi, valamint környezettudományi oktatás...

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Genomics and experimental cardiology research group

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The role of PARP-1 in MPK-1 expression and MAPK pathway activation in oxidative stress. Although PARP-1 is an enzyme found in the nucleus, it affects pathways originating from the cytoplasm, and mitochondria. The length of strands made up of ADP-ribose units catalyzed by PARP-1 can consist of only a few units up to 200 units, which can be disassembled quickly by poly(ADP-ribose) glycohydrolyze (PARG). ADP-ribose units are able to enter the cytoplasm and initiate mitochondrial depolarization, which induces the emission of apoptosis induction factor (AIF) as a result of oxidative stress. Studies show that nuclear PARP-1 induced ADP-riboslation and ADP-ribose units form contact with the nucleus, cytoplasm, mitochondria and cell receptors, however there is little information regarding the mechanisms behind this. During our research we inhibited PARP-1 enzyme with specific inhibitors, with the help of PARP1 siRNA technology, which resulted in the inhibition of MAP kinase. Our results proved that PARP-1 activated by free radicals regulate the activation of JNK and p38 MAP kinase. The inhibition of JNK and p38 MAP kinase was affected by the elevated levels of cytoplasmic MKP-1, which was induced byPARP-1 inhibition as a result of oxidative stress. Further results showed that as a result of the inhibition of MPK-1, the inhibition of the protective effect of PARP-1 disappeared, which shows the importance of JNK and p38MAP kinase in oxidative stress induced cell death, and furthermore the protective effect of the elevated levels of MPK-1on PARP-1 inhibition. Our results suggest that through the regulation of proteins, nuclear PARP-1 can directly affect mechanisms transmitted towards the cytoplasm.

The role of poly-ADP-ribose polymerase (PARP-1) in cardiovascular regeneration.

The activation of PI3K-Akt pathway has an important role in myocardial regeneration, earlier data shows that the inhibition of PARP enzyme activates PI3K-Akt pathway, and protects the cells from the induction of mitochondrial cell death, thus these processes play an important roles in regeneration.

As a model for chronic heart damage we used hypertensive rats, we examined the effect of PARP inhibitor compounds on heart function and regenerative processes.

  • Richter Gedeon zRt., mass spectrometry proteomic studies, development of protein database (2009)
  • Ngene, mass spectrometry proteomic studies, protein database, conference lectures, publications
  • Bionorica (Germany), LC-MS analytical studies, publications (2008)
  • Polgár Bor Kft., LC-MS analytical and biochemical studies, conference lectures, publications
  • Bock Kft. LC-MS analytical and biochemical studies, conference lectures, publications
  • Patents, protocols, collaboration research
  • Mass spectrometry and chromatography readings
  • Proteomic methods
  • HPLC, nanoLC, UHPLC, MALDI-TOF/TOF, ESI(APCI)-IT MS, ESI(Chip)-QQQ MS, NMR/µMRI
  • Cell culture laboratory
  • Fluorescence microscope
  • Flow cytometry studies
  • Proteomic studies