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. Nom, prénom: PANTARU épouse ENOIU Milica Nature de la thèse: cotutelle France Roumanie Doctorat de l

G. La-deuxième-partie-met-en-Évidence-le-rôle-irréfutable-de-la and G. Dans-la-perexydation-par-iii-système, Cette conclusion est assurée, dans le cas de l'acide linoléïque ou linolénique, principalement par la caractérisation par CLHP et spectrométrie de masse de plusieurs dérivés aldéhydiques Parmi ces derniers, nous avons identifié en plus de l'aldéhyde malonique, le 4-hydroxynonénal (HNE) ainsi que plusieurs aldéhydes insaturés et hydroxyles. Enfin, la troisième partie de ce travail a été consacrée au rôle de 1:11 GGT et de la GGT-rel dans le mêtabolisme dn conjuguê GS-I'I!.'OE (glutathion-c-hydroxynonénal) et a établi que ce dernier est ainsi transformé en CysGly-HNE qui a été identifié par spectrométrie de masse. De plus, nous avons mis en évidence pour la première fois que le métabolisme du GS-HNE dans les cellules exprimant soit la GGT soit la GGT-rel conduit à une augmentation de la cytotoxicité, RDh.! pro-cxidaat al gamm:ll-glulltl!!:lllllil-trl!!Jlil5!fer:ll.:Z:e! ~i gamma-glutamâltransferaze! « related » mperoxidarea .Iipidi,t2 Gamma-glutamiltransferaza (GGT) si gamma-glutamil-transferaza « related, recent descoperità, sunt doua enzime capabile sâ metabolizeze glutationnl (GSH) prin clivarea restului y-glutamil. Lucrarea de fatâa fest întreprinsâ ca urmare a unor studii recente carl' sugereazâ un rol pro-oxidant al GGT în cursul metabolizërii GSH in prezentâ de fer

. Obiectivul and . Este, iar pl' de altâ parte, sà verificàm în ce mâsurâ GGT -rel poate avea un rol similar In prima parte a lucrârii, am demonstrat prin spectrofluorimetrie di formarea de specii reacrive de oxigen in cursul metabolizârii GSH într-un model celular este legatâ direct . . fie de activitatea GGT, fie de activitatea GOT-rel, Cea de a doua parte. pune in evidentâ rolul indiscutabil al GGT in peroxidarea acizilor grasi polinesaturati de câtre ststemul GGT/GSHlFe 3 +. Aceastà concluzie este sustinutâ prin caracterizarea in HPLC si spectrometrie de masâ a mai multor compusi aldehidici formati prin oxidarea acizilor linoleic si Iinolenic. Printre compusii caracterizati, pe lângâ aldehida malonicâ, am identificat 4-hidroxinonenalul (HNE) precum si mai multe aldehide nesaturate si hidroxilate. In sfârsit, in cea de a treia parte, consacratâ studierii rolului GGT si GGT-rel in metabolismul conjugatulul GS-HNE (glutation-d-hidroxinonenal), am stabilit ca acesta din urmà este transformat in CysGly-HNE, compus care a fost identificat in spectrometrie de masà, sa stabilim locul pl' care GGT îl ocupâ în stresul oxidatif plus, pentru prima data, am pus evidentà ca metabolismul GS-HNE în celulele carl' exprima fie GGT, fie GGT-rel