Reaktív nitrogén intermedierek által indukált poli(ADP-ribóz) polimeráz és mátrix metalloproteináz aktiváció vizsgálata in vitro és in vivo

A tétel rövid nézete
dc.contributor.advisorVirág, László
dc.contributor.authorBai, Péter
dc.contributor.departmentDE -- Orvos- és Egészségtudományi Centrum -- Általános Orvostudományi Kar -- Orvosi Vegytani Intézeten
dc.contributor.departmentElméleti orvostudományok doktori iskolahu
dc.date.accessioned2006-12-19T10:14:25Z
dc.date.available2006-12-19T10:14:25Z
dc.date.created2003
dc.date.defended2004-01-09
dc.date.issued2006-12-19T10:14:25Z
dc.description.abstractThe characterisation of the biological effects of reactive nitrogen intermediates (RNIs) is an ever-growing area in the field of free radical research. The best characterised RNI is peroxynitrite (ONOO-) formed in the reaction of superoxide and nitric-oxide. ONOO- is capable of nitrating tyrosil residues of proteins, and of breaking the strands of DNA. Enhanced ONOO- production have been detected under different oxidative stress associated pathological states. DNA strand breaks lead to the activation of poly(ADP-ribose) polymerase (PARP), resulting in oncosis due to collapse of the cellular energetic system. PARP inhibition switches oncosis to apoptosis. In our experiments, the cytotoxicity of nitroxyl was investigated. Nitroxyl treatment in thymocytes leads to DNA single strand breaks and mitochondrial dysfunction. Cytotoxicity was attenuated by PARP inhibition, which was accompanied with the switching of the markers of cell death from oncotic to apoptotic (DNA fragmentation, caspase-3 activation, phosphatidyl-serine exposure). Nitroxyl-induced cytotoxicity was partially dependent on PARP activation, however our experiments suggest the dominance of PARP-independent pathways. We have also investigated the possible role of RNIs and PARP inhibition in doxorubicin-induced cardiotoxicity. Doxorubicin treatment lead to increased nitrotyrosine staining, indicative of peroxinitrite formation. Doxorubicin treatment lead to cardiac muscle cell death, as indicated by increased levels of marker enzymes as CK and LDH. Both PARP inhibition by PJ34 and RNI decomposition by FP15 prevented cardiotoxicity. As a possible novel pathway of cardiotoxicity we have described matrix metalloproteinase (MMP) activation in the heart after doxorubicine treatment. The induction of the newly described MMP was mediated by oxidants. Our results support the pathological significance of the RNI-DNA strand break-PARP activation-oncosis pathway in doxorubicin-induced cardiotoxicity. We also proposed the role of free radical activated MMPs in doxorubicin-induced cardiotoxicity.en
dc.description.degreePhDen
dc.format.extent86, [23] pen
dc.format.extent328043 bytes
dc.format.extent190905 bytes
dc.format.extent2097625 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypeapplication/pdf
dc.format.mimetypeapplication/pdf
dc.identifier.opachttp://webpac.lib.unideb.hu:8082/WebPac/CorvinaWeb?action=cclfind&resultview=longlong&ccltext=idno+bibKLT00363624
dc.identifier.urihttp://hdl.handle.net/2437/443
dc.languagehunhu
dc.language.isohuen
dc.language.isoenen
dc.rightsno_restrictionen
dc.subject.disciplineElméleti orvostudományokhu
dc.subject.dspaceDEENK Témalista::Orvostudomány::Orvosi vegytanhu
dc.subject.meshFree Radicalsen
dc.subject.meshReactive Nitrogen Speciesen
dc.subject.meshPeroxynitrous Aciden
dc.subject.meshNitric Oxideen
dc.subject.meshCell Deathen
dc.subject.meshMatrix Metalloproteinasesen
dc.subject.meshDoxorubicin -- adverse effectsen
dc.subject.meshPoly(ADP-ribose)Polymerasesen
dc.subject.meshNitrogen Oxides -- toxicityen
dc.subject.sciencefieldOrvostudományokhu
dc.titleReaktív nitrogén intermedierek által indukált poli(ADP-ribóz) polimeráz és mátrix metalloproteináz aktiváció vizsgálata in vitro és in vivoen
dc.title.subtitleegyetemi doktori (Ph.D.) értekezésen
dc.title.translatedThe Biological Role of Reactive Nitrogen Intermadiate - Induced Poly (ADP-Ribose) Polymerase and Matrix Metalloproteinase Activationen
Fájlok
Eredeti köteg (ORIGINAL bundle)
Megjelenítve 1 - 3 (Összesen 3)
Nem elérhető
Név:
Bai_Peter_ertekezes.pdf
Méret:
2 MB
Formátum:
Adobe Portable Document Format
Letöltés
Nem elérhető
Név:
Bai_Peter_tezis_angol.pdf
Méret:
186.43 KB
Formátum:
Adobe Portable Document Format
Letöltés
Nem elérhető
Név:
Bai_Peter_tezis_magyar.pdf
Méret:
320.35 KB
Formátum:
Adobe Portable Document Format
Letöltés
Gyűjtemények
Molekuláris Orvostudomány Doktori Iskola