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N-glikozilacija proteina odnosi se na kovalentnu modifikaciju proteina važnu za njihovo pravilno smatanje i funkciju. Promjene u glikozilaciji membranskih proteina predstavljaju prvu frontu odgovora stanice na izmijenjeni okoliš, modificirajući signalne putove i samu fiziologiju stanice. Također, membranski glikoproteini čine ključan dio u prepoznavanju i reakciji na patogene i čimbenike imunološkog sustava. Epigenetički mehanizmi uključeni u ekspresiju gliko-gena (geni uključeni u N-glikozilaciju) predstavljaju jedan od načina regulacije sinteze glikana (nukleotida šećera) te time i cjelokupnog procesa glikozilacije proteina. Cilj ovog istraživanja je odrediti učinak modulacije epigenetičke informacije na ekspresiju N-vezanih površinskih glikana HeLa stanica, upotrebom epigenetičkih inhibitora DNA metiltransferaza i histonskih deacetilaza, te ispitati reverzibilnost izazvanih promjena N-glikoma. S obzirom da glikani membranskih proteina mogu odražavati tumorski i metastatski potencijal stanica, upotreba epigenetičkih inhibitora, čije djelovanje dovodi do promjena u ekspresiji površinskih glikana, bi mogla imati važnu ulogu u terapiji tumora. N-glysoylation is a covalent modification of a protein important for its proper folding and function. Since cell surface represents the first front in cell-to-cell communication and communication between the cell and its environment, surface glycosylation can reflect changes in the environment as well as modify cellular signaling, recognition and adaptive changes in reaction to pathogens and factors of immune system. Changes in expression of glyco-genes through variety of epigenetic mechanisms represent one aspect of regulating glycan synthesis and protein glycosylation. To address the questions regarding the role of epigenetic information in N-glycoslylation, we studied changes in surface N-glycome of HeLa cells upon treatment with epigenetic inhibitors of DNA methyltransferases and histone deacetylasesas as well as reversibility of altered N-glycan profile. Since epigenetic inhibitors are currently explored as therapeutics in treatment of cancer, the presented work contributes to our understanding of their efficiency in altering the N-glycan profile of cancer cells. |
